Faculty Bibliography

BACKGROUND:Survival in pancreatic cancer remains poor with curative potential dependent on operative resection. We reviewed national adherence to practice guidelines to evaluate regional variation in the treatment and survival of patients with pancreatic cancer. METHODS:Retrospective cohort review of adults with pancreatic adenocarcinoma using the National Cancer Data Base from 2006 to 2013. Overall survival was compared by the Kaplan-Meier method and Cox proportional hazards models. Sequential multivariate logistic regression models were generated for odds of: a) diagnosis in stage I/II, b) resection, and c) receipt of multimodality therapy, defined as operative resection plus chemotherapy with or without radiation. Five geographic regions of the United States were used for analyses. RESULTS:A total of 115,952 patients were identified. At least 22% of patients in all stages received no treatment, with only 38.4% and 32.3% of stage I and II patients receiving multimodality therapy. On unadjusted analysis, the Northeast had the greatest survival for all stages of disease, most pronounced for stage I where patients lived 2 to 3 more months (log-rank P < .0001). While adjusted odds of early diagnosis and resection were comparable or greater across regions relative to the Northeast, patients who underwent resection in the Northeast were significantly more likely to receive multimodality therapy. Multivariate Cox modeling for patients receiving multimodality therapy accounted for differences in 3 of 4 remaining regions. CONCLUSION:Regional variations exist in pancreatic cancer treatment and survival. While providing multimodality cancer-directed therapy can help mitigate these differences, survival with pancreatic cancer needs to be interpreted in the context of overall health, underlying risk factors, and life expectancy.

PURPOSE/OBJECTIVE:Stereotactic radiation therapy (SRT) enables focused, short course, high dose per fraction radiation delivery to brain tumors that are less ideal for single fraction treatment because of size, shape, or close proximity to sensitive structures. We sought to identify optimal SRT treatment regimens for maximizing local control while minimizing morbidity. METHODS AND MATERIALS/METHODS:We performed a retrospective review of patients treated with SRT for solid brain metastases using variable dose schedules between 2001 and 2011 at 3 academic hospitals. Endpoints included (1) local control, (2) acute toxicity (Common Toxicity Criteria for Adverse Events v3.0), and (3) symptomatic radionecrosis. Kaplan-Meier and a competing risks methodology were used to estimate the actuarial rate of local failure and assess the association of clinical and treatment covariates with time to local failure. RESULTS:= .01, adjusted hazards ratio, 0.87). Five patients experienced seizures within 10 days of SRT and 5 patients developed radionecrosis. All patients with documented radionecrosis received prior radiation to the index lesion. CONCLUSIONS:Our series of SRT for brain metastases found total prescription dose to be the only factor associated with local control. Both acute and long-term toxicity events from SRT were modest.

Brain metastases are relatively uncommon in gynecological malignancies, and there is limited available data on their management. The present study reports the outcomes of patients with brain metastasis from gynecological malignancies who were treated with stereotactic radiosurgery (SRS). Patients with brain metastasis from a gynecological primary site were treated with SRS using the Cyberknifeâ„¢ frameless SRS system. Primary lesions were treated with a single fraction of 16-22 Gy. A total of 3 resection cavities were treated with 8 Gy 3 times, meaning a total of 24 Gy, and 1 recurrent lesion was re-irradiated with 5 Gy 5 times, meaning a total of 25 Gy. All patients were followed up with regular magnetic resonance imaging and clinical examinations 1 month after treatment and every 2 months thereafter. A total of 20 lesions in 8 patients were included in this study; 1 patient presented with metastatic endometrial cancer and the remaining 7 presented with metastatic ovarian cancer. The median age was 61 years (range, 48-78 years). All patients had received systemic therapy prior to developing brain metastasis. A total of 3 patients underwent surgical resection and 1 patient was administered re-irradiation for recurrence. There were 3 local failures in 2 patients. The actuarial 1-, 2- and 3-year local control rates were 91, 91 and 76%, respectively. The median overall survival time was 29 months. No SRS-associated toxicities or neurological mortalities were observed. In conclusion, brain metastasis from gynecological malignancies is uncommon, however, SRS is a safe and effective treatment modality for local control as a primary or adjuvant treatment in patients with this disease.

PURPOSE/OBJECTIVE(S)/OBJECTIVE:The risk of developing symptomatic edema or seizure following stereotactic radiosurgery (SRS) is poorly defined, and many practitioners prescribe prophylactic corticosteroids and/or anticonvulsants. Because there are no clear guidelines regarding appropriate use, we sought to characterize prescribing practices and factors associated with these recommendations. METHODS AND MATERIALS/METHODS:We conducted a 1-time, internet-based survey among 500 randomly selected radiation oncologists self-described as specializing in central nervous system diseases who were registered in the American Society for Radiation Oncology directory. Physicians were contacted by e-mail and invited to complete the 22-question survey. RESULTS:The response rate was 32% (n = 161). Sixty-six percent of respondents had been in practice for >10 years, and 45% of respondents practiced at an academic medical center. During/after SRS, 53% of respondents "always" or "usually" recommended corticosteroids, whereas 47% "never," "rarely," or "sometimes" recommended them. When prescribing corticosteroids, the recommended duration of use was <1 week, 1-2 weeks, or >2 weeks among 49%, 33%, and 18% of respondents, respectively. Respondents who worked in an academic medical center were less likely to prescribe corticosteroids, although this did not reach significance (P = .09). Seizure prophylaxis was less common overall, as 79% of respondents "rarely" or "never" prescribed anticonvulsants for SRS. Respondents who prescribed anticonvulsants more frequently had higher estimations of the risk of seizure within 2 weeks of SRS (P < .001), and their recommended duration of anticonvulsant use was <1 week, 1-2 weeks, and >2 weeks among 35%, 25%, and 41% of respondents, respectively. CONCLUSIONS:There is extreme variation in physician recommendations regarding prophylactic corticosteroid and anticonvulsant use for patients undergoing SRS. Further investigation of the risks and benefits of these medications for SRS is warranted, which may promote guideline development and more patient-centered, rational prescribing practices.

BACKGROUND:The incidence of positive margins after neoadjuvant chemoradiation and adequate surgery is very low. However, when patients do present with positive or close margins, they are at a risk of local failure and local therapy options are limited. We evaluated the role of stereotactic body radiotherapy (SBRT) in patients with positive or close margins after induction chemoradiation and total mesorectal excision. METHODS:This is a retrospective evaluation of patients treated with SBRT after induction chemoradiation and surgery for positive or close margins. Seven evaluable patients were included. Fiducial seeds were place at surgery. The Cyberknife(TM) system was used for planning and treatment. Patients were followed 1 month after treatment and 3-6 months thereafter. Descriptive statistics and Kaplan-Meir method was used to repot the findings. RESULTS:Seven patients (3 men and 4 women) were included in the study with a median follow-up of 23.5 months. The median initial radiation dose was 5,040 cGy (in 28 fractions) and the median SBRT dose was 2,500 cGy (in 5 fractions). The local control at 2 years was 100%. The overall survival at 1 and 2 years was 100% and 71% respectively. There was no Grade III or IV toxicity. CONCLUSIONS:SBRT reirradiation is an effective and safe method to address positive or close margins after neoadjuvant chemoradiation and surgery for rectal cancer.

AIM/OBJECTIVE:To provide a multi-institutional consensus document for stereotactic body radiotherapy of primary renal cell carcinoma. MATERIALS & METHODS/METHODS:Eight international institutions completed a 65-item survey covering patient selection, planning/treatment aspects and response evaluation. RESULTS:All centers treat patients with pre-existing hypertension and solitary kidneys. Five institutions apply size constraints of 5-8 cm. The total planning target volume expansion is 3-10 mm. All institutions perform pretreatment imaging verification, while seven institutions perform some form of intrafractional monitoring. Number of fractions used are 1-12 to a total dose of 25 Gy-80 GyE. Imaging follow-up for local tumor response includes computed tomography (n = 8), PET-computed tomography (n = 1) and MRI (n = 5). Follow-up frequency is 3-6 months for the first 2 years and 3-12 months for subsequent 3 years. CONCLUSION/CONCLUSIONS:Key methods for safe implementation and practice for stereotactic body radiotherapy kidney have been identified and may aid standardization of treatment delivery.

Adjuvant chemotherapy plays a critical role in the treatment of resected pancreatic cancer patients. However, the role of adjuvant radiation remains controversial. This study compares survival between resected pancreatic cancer patients who received adjuvant radiation and no adjuvant radiation. Medical records of patients with pancreatic ductal adenocarcinoma who underwent surgical resection from January 2003 through 2013 at medical centers in Boston and Leiden were retrospectively reviewed. Propensity score matching was used to correct for potential selection bias in the allocation of adjuvant chemoradiation versus chemotherapy alone. Three hundred fifty total patients were identified, of whom 138 (39.4%) received adjuvant radiation. On pathological staging, 245 (70.0%) had positive lymph nodes, and these patients gained a significant survival benefit from adjuvant radiation (hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.56-0.99) in the complete cohort. After propensity score matching, adjuvant radiation lost its prognostic significance in the complete cohort. However, after matching, patients who survived longer than 12 months and had positive lymph nodes (n = 108) demonstrated a significant (log-rank p = 0.04) survival benefit from adjuvant radiation. This study, while non-randomized, suggests that adjuvant radiation may be associated with a survival benefit for resected pancreatic cancer patients in specific situations.

OBJECTIVES/OBJECTIVE:After adjuvant or definitive radiation for pancreas cancer, there are limited conventional treatment options for recurrent pancreas cancer. We explored the role of (Stereotactic Body Radiotherapy) SBRT for reirradiation of recurrent pancreas Cancer. METHODS:This is a retrospective study of patients reirradiated with SBRT for recurrent pancreas cancer. All patients were deemed unresectable and treated with systemic therapy. Fiducial gold markers were used. CT simulation was performed with oral and IV contrast and patients were treated with respiratory motion tracking in the Cyberknife(TM) system. RESULTS:30 patients (17 men and 13 women) with a median age of 67 years were included in the study. The median target volume was 41.29cc. The median prescription dose was 25Gy (24-36Gy) in a median of 5 fractions prescribed to a mean 78% isodose line. The median overall survival was 14 months. The 1 and 2 year local control was 78%. The worst toxicity included 3/30(10%) Grade III acute toxicity for pain, bleeding and vomiting. There was 2/30 (7%) Grade III long-term bowel obstructions. CONCLUSIONS:SBRT can be a useful and tolerable option for patients with recurrent pancreas cancer after prior radiation.

BACKGROUND:Whole brain radiation therapy (WBRT) is widely used for the treatment of brain metastases. Cognitive decline and alopecia are recognized adverse effects of WBRT. Recently hippocampus sparing whole brain radiation therapy (HS-WBRT) has been shown to reduce the incidence of memory loss. In this study, we found that multi-field intensity modulated radiation therapy (IMRT), with strict constraints to the brain parenchyma and to the hippocampus, reduces follicular scalp dose and prevents alopecia. METHODS:Suitable patients befitting the inclusion criteria of the RTOG 0933 trial received Hippocampus sparing whole brain radiation. On follow up, they were noticed to have full scalp hair preservation. 5 mm thickness of follicle bearing scalp in the radiation field was outlined in the planning CT scans. Conventional opposed lateral WBRT radiation fields were applied to these patient-specific image sets and planned with the same nominal dose of 30 Gy in 10 fractions. The mean and maximum dose to follicle bearing skin and Dose Volume Histogram (DVH) data were analyzed for conventional and HS-WBRT. Paired t-test was used to compare the means. RESULTS:All six patients had fully preserved scalp hair and remained clinically cognitively intact 1-3 months after HS-WBRT. Compared to conventional WBRT, in addition to the intended sparing of the Hippocampus, HS-WBRT delivered significantly lower mean dose (22.42 cGy vs. 16.33 cGy, p < 0.0001), V24 (9 cc vs. 44 cc, p < 0.0000) and V30 (9 cc vs. 0.096 cc, p = 0.0106) to follicle hair bearing scalp and prevented alopecia. There were no recurrences in the Hippocampus area. CONCLUSIONS:HS-WBRT, with an 11-field set up as described, while attempting to conserve hippocampus radiation and maintain radiation dose to brain inadvertently spares follicle-bearing scalp and prevents alopecia.

The initial treatment for primary and locoregional melanoma is surgery. Systemic therapy, and more recently immune therapy, has been the mainstay in the adjuvant and particularly the metastatic setting. Aside from palliation, there is a limited role for definitive radiation therapy for melanoma. However, in the adjuvant setting, postoperative radiation can improve locoregional disease control, albeit with potential toxicity and limited survival benefit. Stereotactic radiosurgery plays a vital role in the treatment of limited brain and extracranial metastasis.