Stereotactic Brachytherapy With Iodine-125 Seeds for the Treatment of Inoperable Low-Grade Gliomas in Children: Long-Term Outcome

.                 Maximilian I. Ruge⇓, Thorsten Simon, Bogdana Suchorska, Ralph Lehrke, Christina Hamisch, Friederike Koerber, Mohammad Maarouf, Harald Treuer, Frank Berthold, Volker Sturm and Jürgen Voges

+

Author Affiliations

.                 Maximilian I. Ruge, Thorsten Simon, Christina Hamisch, Friederike Koerber, Mohammad Maarouf, Harald Treuer, Frank Berthold, and Volker Sturm, University of Cologne, Cologne; Bogdana Suchorska, University of Munich, Munich; Ralph Lehrke, St. Barbara Hospital Hamm, Hamm; and Jürgen Voges, University of Magdeburg. Magdeburg, Germany.

.                 Corresponding author: Maximilian I. Ruge, MD, PhD, University Hospital of Cologne, Main Clinic Building, 11th Floor, Kerpener Straße 62, Cologne, Germany 50937; e-mail: maximilian.ruge@uk-koeln.de.

Abstract

Purpose Resection is generally considered the gold standard for treatment of low-grade (WHO grades I and II) gliomas (LGGs) in childhood. However, approximately 30% to 50% of these tumors are inoperable because of their localization in highly eloquent brain areas. A few reports have suggested stereotactic brachytherapy (SBT) with implantation of iodine-125 (¹²⁵I) seeds as a safe and effective local treatment alternative. This single-center study provides a summary of the long-term outcome after SBT in one of the largest reported patient series.

Patients and Methods All pediatric patients treated with SBT (¹²⁵I seeds; cumulative therapeutic dose 50-65 Gy within 9 months) by our group for LGG with follow-up of more than 6 months were included. Clinical and radiologic outcome, time to progression, and overall survival were evaluated. Prognostic factors (age, sex, Karnofsky performance score, tumor volume, and histology) for survival and disease progression were investigated.

Results In all, 147 of 160 pediatric patients treated with SBT (from 1982 through 2009) were analyzed in detail. Procedure-related mortality was zero, and the 30-day morbidity was transient and low (5.4%). Survival rates at 5 and 10 years were 93%, and 82%, respectively, with no significant difference between WHO grades I and II tumors (median follow-up, 67.1 ± 57.7 months). Twenty-one (14.8%) of 147 patients presented with tumor relapse. The remaining 126 patients revealed complete response in 24.6%, partial response in 31.0%, and stable disease in 29.6%. Neurologic status improved (57.8%) or remained stable (23.0%). None of the evaluated factors had significant impact on the study’s end points except tumor volume more than 15 mL, which caused significantly higher rates of tumor recurrence (P < .05).

Conclusion We demonstrate that SBT represents a safe, minimally invasive, and highly effective local treatment option for pediatric patients with inoperable LGG WHO grades I and II.

Salvage stereotactic radiosurgery for breast cancer brain metastases^†

Outcomes and prognostic factors

Paul J. Kelly MB^1,2,*,‡, Nancy U. Lin MD^2,3, Elizabeth B. Claus MD, PhD^2,4,5, Eudocia C. Quant MD, MPH^2,6, Stephanie E. Weiss MD^1,2, Brian M. Alexander MD, MPH^1,2

Article first published online: 14 SEP 201

Keywords:

salvage;stereotactic radiosurgery;breast cancer;brain metastases;radiation

Abstract

BACKGROUND:

Salvage stereotactic radiosurgery (SRS) is often considered in breast cancer patients previously treated for brain metastases. The goal of this study was to analyze clinical outcomes and prognostic factors for survival in the salvage setting.

METHODS:

The authors retrospectively examined 79 consecutive breast cancer patients who received salvage SRS (interval of >3 months after initial therapy), 76 of whom (96%) received prior whole-brain radiation therapy. Overall survival (OS) and central nervous system (CNS) progression-free survival rates were calculated from the date of SRS using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazards model.

RESULTS:

Median age was 50.5 years. Fifty-eight percent of this population was estrogen receptor positive, 62% was HER2 positive, and 10% was triple negative. At the time of SRS, 95% had extracranial metastases, with 81% of extracranial metastases at other visceral sites (lung/pleura/liver). Forty-eight percent had stable extracranial disease. Median interval from initial brain metastases therapy to SRS was 8.4 months. Median CNS progression-free survival after SRS was 5.7 months (interquartile range [IQR], 3.6-11 months), and median OS was 9.8 months (IQR, 3.8-18 months). Eighty-two percent of evaluable patients received further systemic therapy after SRS. HER2 status (adjusted hazard ratio [HR], 2.4; P = .008) and extracranial disease status (adjusted HR, 2.7; P = .004) were significant prognostic factors for survival on multivariate analysis.

CONCLUSIONS:

In patients with good Karnofsky performance status, salvage SRS for breast cancer brain metastases is a reasonable treatment option, given an associated median survival in excess of 9 months. Furthermore, patients with HER2-positive tumors at diagnosis or stable extracranial disease at the time of SRS have an improved clinical course, with median survival of >1 year. Cancer 2011. © 2011 American Cancer Society.

Radiation Therapy Improves Survival for Patients With Extrapulmonary Small Cell Cancers

May 30, 2011

A recent review article that concentrated on whether surgery and radiation therapy improve survival for patients with extrapulmonary small cell cancers found a significant improvement at both five and 10 years following treatment.

R.A. Grossman and colleagues found 94,173 patients with small cell carcinoma through the Surveillance, Epidemiology and End Results (SEER) database. The authors then categorized the data by site and evaluated survival based on the specific treatment strategy. Of those patients identified, 88,605 (94.1 percent) had small cell carcinoma, and 5,568 (5.9 percent) had EPSCC. The researchers further subdivided the data by site, with genitourinary accounting for 24.1 percent, gastrointestinal for 22.1 percent, head and neck for 7.1 percent, breast for 4 percent and miscellaneous for 42.7 percent.

“Overall, EPSSC and specifically gastrointestinal disease had significantly improved median, five- and 10-year survival with surgery and/or radiation for all stages and sizes,” the researchers stated in the article, “Does Surgery or Radiation Therapy Impact Survival for Patients With Extrapulmonary Small Cell Cancers?” published in the Journal of Surgical Oncology at http://onlinelibrary.wiley.com /doi/10.1002/jso.21976/abstract.

In addition, the researchers discovered several independent predictors of survival: age 50 or older; female gender; a stage of regional or distant; radiation; and surgery.

“Although outcomes for EPSCC remain poor, both surgery and radiation are shown to significantly improve median, five- and 10-year survival rates,” the authors concluded.

ublic release date: 22-Mar-2011

Contact: Anita Srikameswaran

SrikamAV@upmc.edu

412-578-9193

University of Pittsburgh Schools of the Health Sciences

Experimental radioprotective drug safe for lung cancer patients, says Pitt study

PITTSBURGH, March 22 – Patients with advanced non-small cell lung cancer can safely take an experimental oral drug intended to protect healthy tissue from the effects of radiation, according to a study led by researchers at the University of Pittsburgh Cancer Institute (UPCI) and published in this month's issue of Human Gene Therapy.

The findings support further clinical testing of the agent, called manganese superoxide dismutase (MnSOD) plasmid liposome, to determine if giving it alongside chemotherapy and radiation will prevent damage to normal cells that is the typical cause of side effects in cancer treatment, said senior investigator Joel S. Greenberger, M.D., professor and chair, Department of Radiation Oncology, Pitt School of Medicine, and co-director of the lung and esophageal cancer program at UPCI.

"If we can sufficiently protect tissues that are normal, we should be able to deliver our cancer treatments more effectively and perhaps even at higher doses," he explained. "Our aim is to improve the quality of life of patients by minimizing side effects while providing the best treatment for their cancers."

For the safety study, 10 patients with inoperable stage III non-small cell lung cancer took oral doses of MnSOD plasmid liposome twice weekly for a total of 14 doses during seven weeks of conventional chemotherapy and radiation treatment. The agent, which boosts levels of an antioxidant the body makes naturally, is made of fat droplets containing the gene that produces MnSOD. When swallowed, it is absorbed by cells in the esophagus, which is a common site for severe side effects during radiation treatment for lung cancer.

One patient experienced mild heartburn and a slight rash and another had mild constipation and a fluctuation in blood sodium, problems that might be associated with MnSOD treatment. No other toxicities were thought to be due to the experimental drug.

"The results of this initial trial indicate that MnSOD plasmid liposome can be safely administered," Dr. Greenberger said. "It did not linger in normal cells after treatment, nor did it protect cancer cells from radiation treatment. The next study, which is underway at UPCI, is to determine whether it protects normal tissue, particularly the esophagus, from radiation exposure."

A common toxicity of lung cancer radiation therapy is esophagitis, or inflammation of the esophagus, he explained. Within a few weeks of treatment, patients typically experience painful swallowing that over time can become so severe that narcotics or a break from radiotherapy may be necessary for patient comfort.

Preclinical testing has shown that generating higher levels of MnSOD in healthy cells can suppress the production of inflammatory molecules and reduce cell death, micro-ulceration and esophagitis. Because the agent is delivered to healthy tissue, it does not protect tumor cells from radiation treatment. In fact, Dr. Greenberger noted, experiments hint that when it is given to cancer cells, it actually encourages cell death because of abnormalities in their cellular metabolism.

He and his team plan to investigate the use of MnSOD plasmid liposome for other cancers, such as protecting the rectum from radiotherapy for prostate cancer and protecting the bladder during

©American Society of Clinical Oncology

Survival Outcomes After Radiation Therapy for Stage III Non–Small-Cell Lung Cancer After Adoption of Computed Tomography–Based Simulation

+Author Affiliations

From Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA.

Corresponding author: Aileen B. Chen, MD, MPP, Dana-Farber Cancer Institute, 44 Binney St, Smith 255, Boston, MA 02115; e-mail: achen7@partners.org.

Abstract

Purpose Technical studies suggest that computed tomography (CT) –based simulation improves the therapeutic ratio for thoracic radiation therapy (TRT), although few studies have evaluated its use or impact on outcomes.

Methods We used the Surveillance, Epidemiology and End Results (SEER) –Medicare linked data to identify CT-based simulation for TRT among Medicare beneficiaries diagnosed with stage III non–small-cell lung cancer (NSCLC) between 2000 and 2005. Demographic and clinical factors associated with use of CT simulation were identified, and the impact of CT simulation on survival was analyzed by using Cox models and propensity score analysis.

Results The proportion of patients treated with TRT who had CT simulation increased from 2.4% in 1994 to 34.0% in 2000 to 77.6% in 2005. Of the 5,540 patients treated with TRT from 2000 to 2005, 60.1% had CT simulation. Geographic variation was seen in rates of CT simulation, with lower rates in rural areas and in the South and West compared with those in the Northeast and Midwest. Patients treated with chemotherapy were more likely to have CT simulation (65.2% v 51.2%; adjusted odds ratio, 1.67; 95% CI, 1.48 to 1.88; P < .01), although there was no significant association between use of surgery and CT simulation. Controlling for demographic and clinical characteristics, CT simulation was associated with lower risk of death (adjusted hazard ratio, 0.77; 95% CI, 0.73 to 0.82; P < .01) compared with conventional simulation.

Conclusion CT-based simulation has been widely, although not uniformly, adopted for the treatment of stage III NSCLC and is associated with higher survival among patients receiving TRT.

Journal of Thoracic Oncology:

April 2011 - Volume 6 - Issue 4 - pp 688-698

doi: 10.1097/JTO.0b013e31821034ae

Original Articles

Soy Isoflavones Augment Radiation Effect by Inhibiting APE1/Ref-1 DNA Repair Activity in Non-small Cell Lung Cancer

Singh-Gupta, Vinita PhD*; Joiner, Michael C. PhD*; Runyan, Lindsay BSc*; Yunker, Christopher K. BSc*; Sarkar, Fazlul H. PhD†; Miller, Steven MD*; Gadgeel, Shirish M. MD‡; Konski, Andre A. MD*; Hillman, Gilda G. PhD*

Abstract

Introduction: Soy isoflavones sensitize cancer cells to radiation both in vitro and in vivo. To improve the effect of radiotherapy for non-small cell lung cancer, we assessed the potential of using a complementary approach with soy isoflavones.

Methods: Human A549 non-small cell lung cancer cells were treated with soy isoflavones, radiation, or both and tested for cell growth. DNA double-strand breaks (DSBs) were detected by immunostaining for γ-H2AX foci. Expressions of γ-H2AX, HIF-1α, and APE1/Ref-1 were assessed by Western blots. DNA-binding activities of HIF-1α and NF-κB transcription factors were analyzed by electrophoretic mobility shift assay.

Results: Soy isoflavones increased A549 cell killing induced by radiation. Multiple γ-H2AX foci were detectable at 1 hour after radiation but decreased at 24 hours after radiation. Soy isoflavones also caused DNA DSBs, but γ-H2AX foci increased over time. Soy isoflavones and radiation caused an increase in γ-H2AX foci, which persisted at 24 hours, indicating both increased DNA damage and inhibition of repair. Soy isoflavones inhibited the radiation-induced activity of the DNA repair/redox enzyme APE1/Ref-1 and the transcription factors NF-κB and HIF-1α. E3330, which inhibits the redox activity of APE1/Ref-1, did not alter the repair of radiation-induced DSBs. Methoxyamine, which inhibits APE1/Ref-1 DNA repair activity, partly blocked the decrease in radiation-induced DSBs at 24 hours, suggesting partial mitigation of radiation-induced DNA repair akin to the effect of soy combined with radiation, in agreement with cytotoxic assays.

Conclusions: Inhibition of APE1/Ref-1 DNA repair activity by soy could be involved in the mechanism by which soy alters DNA repair and leads to cell killing

The Lancet Oncology,

Volume 12, Issue 4, Pages 353 - 360, April 2011
doi:10.1016/S1470-2045(11)70061-4Cite or Link Using DOI
Published Online: 30 March 2011

Proportion of second cancers attributable to radiotherapy treatment in adults: a cohort study in the US SEER cancer registries

Dr Amy Berrington de Gonzalez DPhil a , Rochelle E Curtis MA a, Stephen F Kry PhD b, Ethel Gilbert PhD a, Stephanie Lamart PhD a, Christine D Berg MD c, Prof Marilyn Stovall PhD b, Prof Elaine Ron PhD a ‡

Summary

Background

Improvements in cancer survival have made the long-term risks from treatments more important, including the risk of developing a second cancer after radiotherapy. We aimed to estimate the proportion of second cancers attributable to radiotherapy in adults with data from the US Surveillance, Epidemiology and End Results (SEER) cancer registries.

Methods

We used nine of the SEER registries to systematically analyse 15 cancer sites that are routinely treated with radiotherapy (oral and pharynx, salivary gland, rectum, anus, larynx, lung, soft tissue, female breast, cervix, endometrial, prostate, testes, eye and orbit, brain and CNS, and thyroid). The cohort we studied was composed of patients aged 20 years or older who were diagnosed with a first primary invasive solid cancer reported in the SEER registries between Jan 1, 1973, and Dec 31, 2002. Relative risks (RRs) for second cancer in patients treated with radiotherapy versus patients not treated with radiotherapy were estimated with Poisson regression adjusted for age, stage, and other potential confounders.

Findings

647 672 cancer patients who were 5-year survivors were followed up for a mean 12 years (SD 4·5, range 5—34); 60 271 (9%) developed a second solid cancer. For each of the first cancer sites the RR of developing a second cancer associated with radiotherapy exceeded 1, and varied from 1·08 (95% CI 0·79—1·46) after cancers of the eye and orbit to 1·43 (1·13—1·84) after cancer of the testes. In general, the RR was highest for organs that typically received greater than 5 Gy, decreased with increasing age at diagnosis, and increased with time since diagnosis. We estimated a total of 3266 (2862—3670) excess second solid cancers that could be related to radiotherapy, that is 8% (7—9) of the total in all radiotherapy patients (≥1 year survivors) and five excess cancers per 1000 patients treated with radiotherapy by 15 years after diagnosis.

Interpretation

A relatively small proportion of second cancers are related to radiotherapy in adults, suggesting that most are due to other factors, such as lifestyle or genetics.

Funding

US National Cancer Institute.

The Lancet Oncology, Early Online Publication, 25 March 2011

doi:10.1016/S1470-2045(11)70063-8Cite or Link Using DOI

Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial

Prof James W Denham MD a , Allison Steigler BMath a, Prof David S Lamb FRANZCR b, Prof David Joseph FRANZCR c, Sandra Turner FRANZCR d, John Matthews FRANZCR e, Chris Atkinson FRANZCR f, John North FRANZCR g, David Christie FRANZCR h, Prof Nigel A Spry FRANZCR c, Keen-Hun Tai FRANZCR i, Chris Wynne FRANZCR f, Prof Catherine D'Este PhD j

Summary

Background

The TROG 96.01 trial assessed whether 3-month and 6-month short-term neoadjuvant androgen deprivation therapy (NADT) decreases clinical progression and mortality after radiotherapy for locally advanced prostate cancer. Here we report the 10-year results.

Methods

Between June, 1996, and February, 2000, 818 men with T2b, T2c, T3, and T4 N0 M0 prostate cancers were randomly assigned to receive radiotherapy alone, 3 months of NADT plus radiotherapy, or 6 months of NADT plus radiotherapy. The radiotherapy dose for all groups was 66 Gy, delivered to the prostate and seminal vesicles (excluding pelvic nodes) in 33 fractions of 2 Gy per day (excluding weekends) over 6·5—7·0 weeks. NADT consisted of 3·6 mg goserelin given subcutaneously every month and 250 mg flutamide given orally three times a day. NADT began 2 months before radiotherapy for the 3-month NADT group and 5 months before radiotherapy for the 6-month NADT group. Primary endpoints were prostate-cancer-specific mortality and all-cause mortality. Treatment allocation was open label and randomisation was done with a minimisation technique according to age, clinical stage, tumour grade, and initial prostate-specific antigen concentration (PSA). Analysis was by intention-to-treat. The trial has been closed to follow-up and all main endpoint analyses are completed. The trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12607000237482.

Findings

802 men were eligible for analysis (270 in the radiotherapy alone group, 265 in the 3-month NADT group, and 267 in the 6-month NADT group) after a median follow-up of 10·6 years (IQR 6·9—11·6). Compared with radiotherapy alone, 3 months of NADT decreased the cumulative incidence of PSA progression (adjusted hazard ratio 0·72, 95% CI 0·57—0·90; p=0·003) and local progression (0·49, 0·33—0·73; p=0·0005), and improved event-free survival (0·63, 0·52—0·77; p<0·0001). 6 months of NADT further reduced PSA progression (0·57, 0·46—0·72; p<0·0001) and local progression (0·45, 0·30—0·66; p=0·0001), and led to a greater improvement in event-free survival (0·51, 0·42—0·61, p<0·0001), compared with radiotherapy alone. 3-month NADT had no effect on distant progression (0·89, 0·60—1·31; p=0·550), prostate cancer-specific mortality (0·86, 0·60—1·23; p=0·398), or all-cause mortality (0·84, 0·65—1·08; p=0·180), compared with radiotherapy alone. By contrast, 6-month NADT decreased distant progression (0·49, 0·31—0·76; p=0·001), prostate cancer-specific mortality (0·49, 0·32—0·74; p=0·0008), and all-cause mortality (0·63, 0·48—0·83; p=0·0008), compared with radiotherapy alone. Treatment-related morbidity was not increased with NADT within the first 5 years after randomisation.

Interpretation

6 months of neoadjuvant androgen deprivation combined radiotherapy is an effective treatment option for locally advanced prostate cancer, particularly in men without nodal metastases or pre-existing metabolic comorbidities that could be exacerbated by prolonged androgen deprivation.

Funding

Australian Government National Health and Medical Research Council, Hunter Medical Research Institute, AstraZeneca, and Schering-Plough

Ann Oncol (2011)

doi: 10.1093/annonc/mdq695

First published online: February 15, 2011

Male pattern baldness and the risk of prostate cancer

. M. Yassa1, M. Saliou1, Y. De Rycke2, C. Hemery3, M. Henni1, J. M. Bachaud4, N. Thiounn5, J. M. Cosset3 and P. Giraud3,6,^*

Author Affiliations

. ¹Department of Oncology Radiotherapy, European Georges Pompidou Hospital

. ²Department of Biostatistics, Curie Institute

. ³Department of Oncology Radiotherapy, Curie Institute, Paris

. ⁴Department of Oncology Radiotherapy, Claudius Regaud Institute, Toulouse

. ⁵Department of Urology, European Georges Pompidou Hospital

. ⁶Department of Oncology Radiotherapy, European Georges Pompidou Hospital, Paris Descartes University, Paris, France

. ^*Correspondence to: Prof. P. Giraud, Department of Oncology Radiotherapy, European Georges Pompidou Hospital, 20 Rue Leblanc, 75015 Paris, France. Tel: +33-1-56-09-54-65; Fax: +33-1-56-09-25-86; E-mail: philippe.giraud@egp.aphp.fr

Received June 22, 2010.

Revision received August 22, 2010.

Accepted November 2, 2010.

Abstract

Background: Androgens play a role in the development of both androgenic alopecia, commonly known as male pattern baldness, and prostate cancer. We set out to study if early-onset androgenic alopecia was associated with an increased risk of prostate cancer later in life.

Patients and methods: A total of 669 subjects (388 with a history of prostate cancer and 281 without) were enrolled in this study. All subjects were asked to score their balding pattern at ages 20, 30 and 40. Statistical comparison was subsequently done between both groups of patients.

Results: Our study revealed that patients with prostate cancer were twice as likely to have androgenic alopecia at age 20 [odds ratio (OR) 2.01, P = 0.0285]. The pattern of hair loss was not a predictive factor for the development of cancer. There was no association between early-onset alopecia and an earlier diagnosis of prostate cancer or with the development of more aggressive tumors.

Conclusions: This study shows an association between early-onset androgenic alopecia and the development of prostate cancer. Whether this population can benefit from routine prostate cancer screening or systematic use of 5-alpha reductase inhibitors as primary prevention remains to be determined..

RTOG 0529: IMRT Less Toxic, as Effective as Conventional Radiation Therapy Against Anal Cancer Philadelphia, PA - January 19, 2011-Combining chemotherapy with intensity-modulated radiation therapy (IMRT) is just as effective after two years in treating anal cancer as chemotherapy and conventionally delivered radiation therapy, but with fewer significant side effects according to new research presented by the Radiation Therapy Oncology Group (RTOG). The results of an RTOG phase II trial were presented at the eighth annual American Society for Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium in San Francisco, CA. RTOG is a National Cancer Institute-funded national clinical trials group and is administered by the American College of Radiology. "Radiation therapy with concurrent 5-fluorouracil and mitomycin-C chemotherapy serves as the standard of care for patients with non-metastatic squamous cell cancer of the anal canal in the United States," explained lead researcher Lisa Kachnic, MD, chair of radiation oncology at Boston University and principal investigator of RTOG trial 0529. "This treatment results in long- term disease-free survival, but is associated with significant acute toxicity due in part to the large radiation fields used. The use of IMRT may address this problem." In contrast to two or three-dimensional conventional radiation fields, which indiscriminately treat normal organs, IMRT is a novel technology that conforms or "paints" the radiation dose to the tumor and lymph node regions, while sparing healthy surrounding tissues. Improvements in treatment-related toxicity have already been described in patients with breast, head and neck and prostate cancers treated with IMRT, as compared to conventionally delivered radiation therapy. In the current study, Dr. Kachnic and the RTOG analyzed the outcome of 52 stage II and stage III patients with anal cancer treated with IMRT and 5-fluorouracil/mitomycin-C chemotherapy. After a median follow-up of 26.7 months, the two-year disease-free survival was 77 percent, and overall survival was 86 percent. These results were very similar to the 325-patient, 5- fluorouracil/mitomycin-C arm of the RTOG 9811 trial, which used conventionally delivered radiation: 75 percent disease-free survival and 91 percent overall survival at two years. However, the use of IMRT in RTOG 0519 was associated with less skin and gastrointestinal acute toxicity. "Based on RTOG 0529, IMRT with 5-fluorouracil and mitomycin-C is associated with significant sparing of grade three and higher dermatologic and gastrointestinal acute toxicity as compared to the 5-fluorouracil/mitomycin-C and conventionally delivered radiation arm of RTOG 9811, without compromising two year outcomes," said Dr. Kachnic. "IMRT will now serve as the standard radiation technique in future RTOG anal cancer trials assessing novel agents in combination with radiation." # # # ASCO Abstract #368: Two-year outcomes of RTOG 0529: A phase II evaluation of dose-painted IMRT in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal. Authors: L. A. Kachnic, K. A. Winter, R. J. Myerson, M. D. E. Goodyear, J. Willins, J. Esthappan, M. G. Haddock, M. Rotman, P. J. Parikh, C. G. Willett; Boston Medical Center, Boston, MA; ACR/RTOG, Philadelphia, PA; Washington University School of Medicine, St. Louis, MO; Dalhousie University, Halifax, NS; Mayo Clinic, Rochester, MN; SUNY Health Science Center, Brooklyn, NY; Duke University Medical Center, Durham, NC

Brachytherapy for Accelerated Partial-Breast Irradiation: A Rapidly Emerging Technology in Breast Cancer Care

Volume 29, Issue 2 - January 10, 2011

From The University of Texas MD Anderson Cancer Center, Houston, TX; University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ; William Beaumont Hospital, Royal Oak, MI; Medical College of Wisconsin, Milwaukee, WI; Virginia Commonwealth University, Richmond, VA; and Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, MA.

Corresponding author: Ya-Chen T. Shih, PhD, Section of Health Services Research, Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, PO Box 301402, Houston, TX 77030; e-mail:yashih@mdanderson.org.

Presented in part at the 51st Annual Meeting of the American Society of Therapeutic Radiology and Oncology, November 1-5, 2009, Chicago, IL.

Abstract

Purpose Brachytherapy is a method for delivering partial-breast irradiation after breast-conserving surgery (BCS). It is currently used in the community setting, although its efficacy has yet to be validated in prospective comparative trials. Frequency and factors influencing use have not been previously identified.

Methods In a nationwide database of 6,882 Medicare beneficiaries (age ≥ 65 years) with private supplemental insurance (MarketScan Medicare Supplemental), claims codes identified patients treated with brachytherapy versus external-beam radiation after BCS for incident breast cancer (diagnosed from 2001 to 2006). Logistic regression modeled predictors of brachytherapy use.

Results Frequency of brachytherapy use as an alternative to external-beam radiation after BCS increased over time (< 1% in 2001, 2% in 2002, 3% in 2003, 5% in 2004, 8% in 2005, 10% in 2006; P < .001). Increased use correlated temporally with US Food and Drug Administration approval and Medicare reimbursement of brachytherapy technology. Brachytherapy use was more likely in women with lymph node–negative disease (odds ratio [OR], 2.19; 95% CI, 1.17 to 4.11) or axillary surgery (OR, 1.74; 95% CI, 1.23 to 2.44). Brachytherapy use was also more likely in women with non–health maintenance organization insurance (OR, 1.81; 95% CI, 1.24 to 2.64) and in areas with higher median income (OR, 1.58; 95% CI, 1.05 to 2.38), lower density of radiation oncologists (OR, 1.78; 95% CI, 1.11 to 2.86), or higher density of surgeons (OR, 1.57; 95% CI, 1.07 to 2.31).

Conclusion Despite ongoing questions regarding efficacy, breast brachytherapy was rapidly incorporated into the care of older, insured patients. In our era of frequently emerging novel technologies yet growing demands to optimize costs and outcomes, results provide insight into how clinical, policy, and socioeconomic factors influence new technology diffusion into conventional care.

Neurosurgery. 2010 Dec;67(6):1637-45.

Outcome predictors after gamma knife radiosurgery for recurrent trigeminal neuralgia.

Kano H, Kondziolka D, Yang HC, Zorro O, Lobato-Polo J, Flannery TJ, Flickinger JC, Lunsford LD.

1Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 2Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, and Department of Neurosurgery, Taipei Veterans General Hospital, Taipei, Taiwan 3Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

Abstract

BACKGROUND: Trigeminal neuralgia (TN) that recurs after surgery can be difficult to manage.

OBJECTIVE: To define management outcomes in patients who underwent gamma knife stereotactic radiosurgery (GKSR) after failing 1 or more previous surgical procedures.

METHODS: We retrospectively reviewed outcomes after GKSR in 193 patients with TN after failed surgery. The median patient age was 70 years (range, 26-93 years). Seventy-five patients had a single operation (microvascular decompression, n = 40; glycerol rhizotomy, n = 24; radiofrequency rhizotomy, n = 11). One hundred eighteen patients underwent multiple operations before GKSR. Patients were evaluated up to 14 years after GKSR.

RESULTS: After GKSR, 85% of patients achieved pain relief or improvement (Barrow Neurological Institute grade I-IIIb). Pain recurrence was observed in 73 of 168 patients 6 to 144 months after GKSR (median, 6 years). Factors associated with better long-term pain relief included no relief from the surgical procedure preceding GKSR, pain in a single branch, typical TN, and a single previous failed surgical procedure. Eighteen patients (9.3%) developed new or increased trigeminal sensory dysfunction, and 1 developed deafferentation pain. Patients who developed sensory loss after GKSR had better long-term pain control (Barrow Neurological Institute grade I-IIIb: 86% at 5 years).

CONCLUSION: GKSR proved to be safe and moderately effective in the management of TN that recurs after surgery. Development of sensory loss may predict better long-term pain control. The best candidates for GKSR were patients with recurrence after a single failed previous operation and those with typical TN in a single trigeminal nerve distribution

Neurosurgery. 2010 Dec;67(6):1515-22.

The louisiana state university experience in the management of single small cerebellar metastasis.

Javalkar V, Cardenas R, Ampil F, Ahmed O, Shi R, Nanda A.

1Department of Neurosurgery, Louisiana State University Health Sciences Center, Shreveport, Louisiana 2Department of Radiation Oncology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 3Department of Medicine, Louisiana State University Health Sciences Center, Shreveport, Louisiana.

Abstract

BACKGROUND: Cerebellar metastasis is often believed to be a more immediately life-threatening complication than brain metastasis in other locations. It is considered a negative prognostic factor in patients with systemic cancers. Despite its clinical importance and technological advances, the survival outcomes of patients with single small cerebellar metastases are rarely studied.

OBJECTIVE: To retrospectively evaluate our experience in the management of patients with single small cerebellar metastasis and compare the treatment modalities.

MATERIAL AND METHODS: A total of 35 patients with single small cerebellar metastasis were included in this retrospective analysis. Of the 35 patients, 24 had surgery followed by whole-brain radiation therapy and 11 had Gamma Knife radiosurgery alone.

RESULTS: The median survival for the whole cohort was 5.6 months after the intervention. No significant differences were noted in median survival between the surgery plus whole-brain radiation therapy and the Gamma Knife radiosurgery alone groups (6.3 months: 95% confidence interval [CI], 4.0-8.6; vs 5.0 months: 95% CI, 1.9-8.1; P = .9). There was no difference in the median time to local progression, distance progression, and overall progression between the 2 groups. Patients with hydrocephalus had a significantly lower survival rate (median, 3.3 months; 95% CI, 0.0-6.6) compared with those without hydrocephalus (median, 6.9 months; 95% CI, 4.4-9.8; P = .02). In the Cox regression model, the significant predictor of survival was hydrocephalus (P = .01; hazard ratio, 3.5; 95% CI, 1.3-9.1) after propensity score adjustment.

CONCLUSION: Treatment with Gamma Knife radiosurgery alone and surgery plus whole-brain radiation therapy were both efficacious in patients with single small cerebellar metastasis. Overall survival was nearly identical in both treatment groups.

Curr Opin Oncol. 2010 Nov 22. [Epub ahead of print]

Stereotactic radiation therapy: changing treatment paradigms for stage I nonsmall cell lung cancer.

Palma D, Senan S.

aDepartment of Radiation Oncology, VU University Medical Center, Amsterdam, The Netherlands bDepartment of Radiation Oncology, London Regional Cancer Program, University of Western Ontario, London, Ontario, Canada.

Abstract

PURPOSE OF REVIEW: To review recent developments in stereotactic body radiation therapy (SBRT) for stage I nonsmall cell lung cancer (NSCLC).

RECENT FINDINGS: In stage I tumors measuring up to 5 cm in diameter, SBRT can achieve local tumor control rates of up to 97%. SBRT has a favorable toxicity profile and has been safely applied in elderly patients, after previous pneumonectomy, or with severe chronic obstructive airways disease. Population studies indicate that the introduction of SBRT was associated with increased treatment rates for elderly patients and improved overall survival.

SUMMARY: In patients with stage I NSCLC who do not undergo surgery, SBRT achieves superior survival as compared to treatment using conventionally fractionated radiotherapy. The role of SBRT in operable patients remains to be defined within randomized trials. In patients identified to be at high risk for surgical complications, SBRT appears to provide an effective alternative with low risks of hospitalization and 30-day mortality. Future treatment algorithms should include individualized assessment of surgical risks, and the consideration of SBRT for high-risk patients, in order to develop a personalized treatment approach

Strahlenther Onkol. 2010 Oct;186(10):565-571. Epub 2010 Sep 30.

A Comparison of Radiotherapy with Radiotherapy plus Surgery for Brain Metastases from Urinary Bladder Cancer : Analysis of 62 Patients.

Fokas E, Henzel M, Engenhart-Cabillic R.

Department of Radiotherapy and Radiation Oncology, Philipps University Marburg, Marburg, Germany, emmanouil.fokas@yahoo.de.

Abstract

PURPOSE: : To evaluate the role of radiotherapy (RT) and prognostic factors in 62 patients with brain metastases from transitional cell carcinoma (TCC) of the urinary bladder.

PATIENTS AND METHODS: : 62 patients received either RT (n = 49), including whole-brain radiotherapy (WBRT) and/or stereotactic radiosurgery (SRS), or surgery (OP) combined with WBRT (n = 13). Overall survival (OS), intracerebral control (ICC) and local control (LC) were retrospectively analyzed. Six potential prognostic factors were assessed: age, gender, number of brain metastases, extracerebral metastases, recursive partitioning analysis (RPA) class, and interval from tumor diagnosis to RT.

RESULTS: : Median OS and ICC for the entire cohort were 9 and 7 months. No significant difference between RT and OP + RT was found for OS (p = 0.696) and ICC (p = 0.996). On multivariate analysis, improved OS was associated with lack of extracerebral metastases (p < 0.001) and RPA class (p < 0.001), and ICC with the latter (p < 0.001). SRS-incorporating RT resulted in 1-, 2-, and 3-year LC probability of 78%, 66%, and 51%. No association between LC and any of the potential prognostic factors was observed. The results of the subgroup RPA class analyses were similar to the entire cohort.

CONCLUSION: : Patient outcome for the RT-alone arm was not significantly different from OP + RT. SRS-incorporating treatment offers excellent LC rates. RPA class and the presence of extracerebral metastases demonstrated a significant prognostic role for survival. The latter should be used as stratification factors in randomized trials and can help define the cohort of patients that may benefit from more aggressive therapies.

Neurosurg Clin N Am. 2011 Jan;22(1):37-44.

Radiotherapy for brain metastases.

Den RB, Andrews DW.

Department of Radiation Oncology, Thomas Jefferson University, 111 South 11th Street, Bodine Cancer Center, Philadelphia, PA 19107, USA.

Abstract

Brain metastases affect 20% to 40% of patients with cancer and are the most common intracranial tumor in adults. The optimal treatment of brain metastases remains controversial. There are several patient- and treatment-related factors that must be considered to determine the optimal management for a given patient. At present, there is randomized control evidence supporting multiple treatment strategies incorporating radiotherapy.

Published by Elsevier Inc.

Radiother Oncol. 2010 Nov 23. [Epub ahead of print]

T1-2 anal carcinoma requires elective inguinal radiation treatment - The results of Trans Tasman Radiation Oncology Group study TROG 99.02.

Matthews JH, Burmeister BH, Borg M, Capp AL, Joseph D, Thompson KM, Thompson PI, Harvey JA, Spry NA.

Department of Radiation Oncology, Auckland City Hospital, New Zealand.

Abstract

BACKGROUND AND PURPOSE: Elective inguinal irradiation increases morbidity. We describe outcomes of moderate intensity chemoradiation treating anal canal and adjacent pelvic nodes only.

MATERIAL AND METHODS: Forty patients with T1-2, N0 anal carcinoma were enrolled between March 1999 and March 2003. Inguinal nodes were NOT electively irradiated. The anal canal and regional pelvic nodes received 36Gy/20# over 4weeks, and 2weeks later the anal canal was boosted with 14.4Gy/8#. Chemotherapy was 5 fluorouracil 800mg/m(2)/day on days 1-4 and 36-39, and Mitomycin C 10mg/m(2) on day 1.

RESULTS: Median follow-up was 44months. Complete response was 95%. Four year results were; overall survival 71%, local control 82%, and colostomy-free survival (including salvage) 85%. Inguinal failure occurred in 22.5% but was isolated in only 12.5%. Treatment was well tolerated acutely with no toxic deaths. Severe late toxicity occurred in 7.5%.

CONCLUSIONS: This moderate dose 'non inguinal' chemoradiation regimen resulted in modest acute toxicity, minimal long term morbidity and local control in line with other series. However staging failed to identify 12.5% of patients whose isolated inguinal failure might have been prevented by elective irradiation. Without more effective staging, all patients should receive elective inguinal irradiation.

Nature Reviews Clinical Oncology 7, 610 (November 2010) | doi:10.1038/nrclinonc.2010.160

Radiotherapy: NSCLC treatment—reducing costs and improving outcomes

Lisa Richards

Abstract
Increasing evidence has shown that stereotactic body radiotherapy (SBRT) can improve local control rates compared with conventional fractionated radiotherapy (external beam radiotherapy; EBRT) for the treatment of medically inoperable non-small-cell lung cancer (NSCLC). Now, a new study has found that, in addition to improved local control and overall survival, treatment costs associated with SBRT are substantially lower than with EBRT

Head Neck. 2010 Nov 10. [Epub ahead of print]

Complete resolution of laryngeal amyloidosis with radiation treatment.

Neuner GA, Badros AA, Meyer TK, Nanaji NM, Regine WF.

Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland.

Abstract

BACKGROUND.: Localized amyloidosis of the larynx is a rare entity of unclear etiology. Surgical debulking is the primary treatment modality but often is not curative. METHODS AND RESULTS.: A 41-year-old woman presenting with increasing hoarseness, dysphagia, dyspnea, and weight loss was found to have a submucosal mass in the left false vocal fold. Biopsy of the specimen revealed amyloid. After negative work-up for systemic disease, the patient underwent surgical debulking. Specimens revealed a population of clonal plasma cells demonstrating lambda restriction. The patient was treated with adjuvant external beam radiation to a dose of 45 Gy. At 11 months, the patient's voice, breathing, and swallowing have all improved substantially. CONCLUSIONS.: Recent pathologic studies suggest that localized amyloidosis of the larynx is caused by a localized, nonmalignant plasma cell disorder. Because full resection is difficult, we recommend a combination of surgery and radiation therapy to cure this disease. © 2010 Wiley Periodicals, Inc. Head Neck, 2010.

International Journal of Radiation Oncology-Biology-Physics

Volume 78, Issue 1, Pages 1-320 (01 September 2010)

Extrahepatic Bile Duct Cancers: Surgery Alone Versus Surgery Plus Postoperative Radiation Therapy,
Hee Keun Gwak, Woo Chul Kim, Hun Jung Kim, Jeong Hoon Park

Abstract

Purpose

The goal of this study was to determine the role of radiotherapy after curative-intent surgery in the management of extrahepatic bile duct (EHBD) cancers.

Methods and Materials

From 1997 through 2005, 78 patients with EHBD cancer were surgically staged. These patients were stratified by the absence of adjuvant radiation (n = 47, group I) versus radiation (n = 31, group II) after resection. Pathology examination showed 27 cases in group I and 20 cases in group II had microscopically positive resection margins. The patients in group II received 45 to 54 Gy of external beam radiotherapy. The primary endpoints of this study were overall survival, disease-free survival, and prognostic factors.

Results

There were no differences between the 5-year overall survival rates for the two groups (11.6% in group I vs. 21% in group II). However, the patients with microscopically positive resection margins who received adjuvant radiation therapy had higher median disease-free survival rates than those who underwent surgery alone (21 months vs. 10 months, respectively, p =0.042). Decreasing local failure was found in patients who received postoperative radiotherapy (61.7% in group I and 35.6% in group II, p = 0.02). Outcomes of the patients with a positive resection margin and lymph node metastasis who received postoperative radiation therapy were doubled compared to those of patients without adjuvant radiotherapy. Resection margin status, lymph node metastasis, and pathology differentiation were significant prognostic factors in disease-free survival.

Conclusions

Adjuvant radiotherapy might be useful in patients with EHBD cancer, especially for those patients with microscopic residual tumors and positive lymph nodes after resection for increasing local control.

J Clin Oncol. 2010 Nov 1. [Epub ahead of print]

The Future of Radiation Oncology

in the United States

From 2010 to 2020: Will Supply Keep Pace With

Demand?

Smith BD, Haffty BG, Wilson LD, Smith GL, Patel AN, Buchholz TA.

The University of Texas M. D. Anderson Cancer Center, Houston, TX; Yale University School of Medicine, New Haven, CT; and Cancer Institute of New Jersey, New Brunswick, NJ.
Abstract
PURPOSE Prior studies forecasted an incipient shortage of medical oncologists as a result of the aging US population, but the radiation oncology workforce has not been studied. Accordingly, we projected demand for radiation therapy and supply of radiation oncologists in 2010 and 2020 to determine whether a similar shortage may exist for this specialty. METHODS Demand for radiation therapy in 2010 and 2020 was estimated by multiplying current radiation utilization rates (as calculated with Surveillance, Epidemiology, and End Results data) by population projections from the Census Bureau. Supply of radiation oncologists was projected using data from the American Board of Radiology inclusive of current radiation oncologists and active residents, accounting for variation in full-time equivalent status and expected survival by age and sex. Results Between 2010 and 2020, the total number of patients receiving radiation therapy during their initial treatment course is expected to increase by 22%, from 470,000 per year to 575,000 per year. In contrast, assuming that the current graduation rate of 140 residents per year remains constant, the number of full-time equivalent radiation oncologists is expected to increase by only 2%, from 3,943 to 4,022. The size of residency training classes for the years 2014 to 2019 would have to double to 280 residents per year in order for growth in supply of radiation oncologists to equal expected growth in demand. CONCLUSION Demand for radiation therapy is expected to grow 10 times faster than supply between 2010 and 2020. Research is needed to explore strategies to enhance capacity to deliver quality radiation therapy despite increased patient loads.
PMID: 20956628 [PubMed - as supplied by publisher

Extracorporeal irradiated tumor bone: A reconstruction option in diaphyseal Ewing's sarcomas.

Puri A, Gulia A, Agarwal M, Jambhekar N, Laskar S.

Department of Orthopedic Oncology, Tata Memorial Hospital, Mumbai, India.

Abstract

BACKGROUND: Limb salvage in extremity tumors is now established as an oncologically safe option without compromising long-term survival. En bloc resection followed by extracorporeal radiation and reimplantation is a biological reconstruction option in diaphyseal Ewing's sarcomas. We analyzed the results of 12 cases of diaphyseal Ewing's sarcomas treated using this modality.

MATERIALS AND METHODS: Between March 2006 and March 2008, 12 patients with Ewing's sarcoma underwent enbloc resection and reconstruction, with reimplantation of the sterilized tumor bone, after extracorporeal irradiation. There were eight males and four females, with a mean age of 14 years (range 2 to 22 years). The femur was the most common bone involved (n=8) followed by the tibia and the humerus (two cases each). All these patients were non-metastatic at presentation and received chemotherapy as per the existing hospital protocol. The mean length of the bone resected was 20 cm (range 11 to 25 cm). The specimen was irradiated with 50 Gy prior to reimplantation and stabilized with the host bone, using suitable internal fixation. Standard biplanar radiographs were assessed for evidence of union on the follow-up visits. The functional status was assessed using the Musculoskeletal Tumor Society Scoring system at the time of the last follow up. The mean follow up duration was 29 months (range 12 to 57 months).

RESULTS: Two patients (17%) had early infection with graft removal, hence are excluded from any analysis of union, however they are included when analysing complications such as infection. Rest 10 cases were analyzed for bony union at the osteotomy sites. Sixteen (84%) of the 19 osteotomy sites united primarily, without any intervention. Implant failure and non-union was seen at three diaphyseal osteotomy sites. The average time for union of all osteotomy sites was 7.2 months (range 3 to 13 months).The average time for union of the metaphyseal osteotomy sites was 5.9 months (range 3 to 12 months) and of diaphyseal osteotomy sites was 8.3 months (range 4 to 13 months). The mean Musculoskeletal Tumor Society Score was 27 (range 19 to 30) with a mean of 27. Nine of the ten patients with lower limb involvement were independent ambulators without additional aids. At the time of the last review, six patients were free of disease and six patients had died from the disease. There were two recurrences around the operative site. Both were associated with disseminated disease and in both the recurrences were in the soft tissue, away from the irradiated graft.

CONCLUSION: Extracorporeal irradiation is a useful, convenient technique for limb salvage in diaphyseal Ewing's sarcomas when there is reasonable residual bone stock. It is oncologically safe and has good functional results. A radiation dose of 50 Gy for sterilizing the bone ensures adequate tumor kill, while minimizing the deleterious effects on the biomechanical and biological properties of the bone. The use of appropriate implants for adequate internal fixation and supplementary bone grafting at the index surgery may help reduce the need for subsequent additional interventions to achieve union. The limitations of this procedure are that it is not applicable in tumor bones that are structurally weak and in bones with pathological fractures.

Radiother Oncol. 2010 Oct 30. [Epub ahead of print]

Radiological and pathological response following pre-operative radiotherapy for soft-tissue sarcoma.

Roberge D, Skamene T, Nahal A, Turcotte RE, Powell T, Freeman C.

Division of Radiation Oncology, McGill University Heath Center, Canada.

Abstract

PURPOSE: To report radiological and pathological response to neo-adjuvant radiotherapy for extremity and trunk soft-tissue sarcomas.

MATERIALS/METHODS: Fifty patients were identified retrospectively. All patients had MRI imaging pre and post neo-adjuvant external beam radiotherapy. Tumor volumes were measured in 3D on T1 Gadolinium enhanced sequences. Pathological treatment response was quantified in terms of percentage of treatment-related necrosis for each case.

RESULTS: Histopathologic responses to treatment varied from 0% to 100%. The median pathological treatment response was 67.5% for low-grade sarcomas and 50% for high-grade sarcomas. The median decrease in tumor volume was 13.8% for non-myxoid low-grade sarcomas, 82.1% for myxoid liposarcomas and <1% for high-grade sarcomas. A partial response on MRI (volume reduction⩾50%) was highly predictive of a good pathological response (p<0.001). Patients with stable disease on imaging or volumetric progression had wide ranging pathological responses.

CONCLUSIONS: Soft-tissue sarcomas show significant pathological treatment responses in the form of hyaline fibrosis, necrosis and granulation tissue. Despite this, there is minimal early volumetric response to radiation, especially for high-grade tumors. Although radiological partial response was predictive of pathological response, the significance of radiological progression was unclear. Myxoid liposarcoma tumor type was predictive of both pathological and radiological tumor response.

Indian J Orthop. 2010 Oct;44(4):390-6.

Extracorporeal irradiated tumor bone: A reconstruction option in diaphyseal Ewing's sarcomas.

Puri A, Gulia A, Agarwal M, Jambhekar N, Laskar S.

Department of Orthopedic Oncology, Tata Memorial Hospital, Mumbai, India.

Abstract

Oncology (Williston Park). 2010 Aug;24(9):815-23, 828.

Intensity-modulated radiation therapy for anal cancer: toxicity versus outcomes.

Zagar TM, Willett CG, Czito BG.

Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina 27705, USA.

Comment in:

Oncology (Williston Park). 2010 Aug;24(9):828, 830-1.

Abstract

The treatment of cancer of the anal canal has changed significantly over the past several decades. Although the abdominoperineal resection (APR) was the historical standard of care, a therapeutic paradigm shift occurred with the seminal work of Nigro, who reported that anal canal cancer could be treated with definitive chemoradiation, with APR reserved for salvage therapy only. This remains an attractive approach for patients and physicians alike and the standard of care in this disease. Now, nearly four decades later, a similar approach continues to be utilized, albeit with higher radiation doses; however, this strategy remains fraught with considerable treatment-related morbidities. With the advent of intensity-modulated radiation therapy (IMRT), many oncologists are beginning to utilize this technology in the treatment of anal cancer in order to decrease these toxicities while maintaining similar treatment efficacy. This article reviews the relevant literature leading up to the modern treatment of anal canal cancer, and discusses IMRT-related toxicity and disease-related outcomes in the context of outcomes of conventionally treated anal cancer.

Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3):649-55.

Radiation oncology in undergraduate medical education: a literature review.

Dennis KE, Duncan G.

Radiation Oncology Program, British Columbia Cancer Agency, Vancouver, British Columbia, Canada. kdennis@bccancer.bc.ca

Comment in:

Int J Radiat Oncol Biol Phys. 2010 Oct 1;78(2):639; author reply 639.

Abstract

PURPOSE: To review the published literature pertaining to radiation oncology in undergraduate medical education.

METHODS AND MATERIALS: Ovid MEDLINE, Ovid MEDLINE Daily Update and EMBASE databases were searched for the 11-year period of January 1, 1998, through the last week of March 2009. A medical librarian used an extensive list of indexed subject headings and text words.

RESULTS: The search returned 640 article references, but only seven contained significant information pertaining to teaching radiation oncology to medical undergraduates. One article described a comprehensive oncology curriculum including recommended radiation oncology teaching objectives and sample student evaluations, two described integrating radiation oncology teaching into a radiology rotation, two described multidisciplinary anatomy-based courses intended to reinforce principles of tumor biology and radiotherapy planning, one described an exercise designed to test clinical reasoning skills within radiation oncology cases, and one described a Web-based curriculum involving oncologic physics.

CONCLUSIONS: To the authors' knowledge, this is the first review of the literature pertaining to teaching radiation oncology to medical undergraduates, and it demonstrates the paucity of published work in this area of medical education. Teaching radiation oncology should begin early in the undergraduate process, should be mandatory for all students, and should impart knowledge relevant to future general practitioners rather than detailed information relevant only to oncologists. Educators should make use of available model curricula and should integrate radiation oncology teaching into existing curricula or construct stand-alone oncology rotations where the principles of radiation oncology can be conveyed. Assessments of student knowledge and curriculum effectiveness are critical.