The Impact of Radiotherapy Facility Volume on the Survival and Guideline Concordance of Patients With Muscle-invasive Bladder Cancer Receiving Bladder-preservation Therapy.

OBJECTIVES: Higher facility surgical volume predicts for improved outcomes in patients with muscle-invasive bladder cancer (MIBC) who undergo radical cystectomy. We investigated the association between facility radiotherapy (RT) case volume and overall survival (OS) for patients with MIBC who received bladder-preserving RT, and the relationship with adherence to National Comprehensive Cancer Network (NCCN) guidelines for bladder preservation. METHODS: The National Cancer Database was used to identify patients diagnosed with nonmetastatic MIBC from 2004 to 2015 and received RT at the reporting center. Facility case volume was defined as the total MIBC patients treated with RT during the period. Facilities were stratified into high-volume facility (HVF) or low-volume facility at the 80th percentile of RT case volume. OS was assessed using Kaplan-Meier analysis. Rates of compliance with NCCN guidelines regarding the use of transurethral resection of the bladder tumor before RT, planned use of concurrent chemotherapy, and total RT dose were compared. Cox proportional hazard model was used to evaluate predictors of OS. RESULTS: There were 7562 patients included. No differences in age, Charlson-Deyo score, T stage, or node-positive rates were observed between groups. HVFs exhibited greater compliance with NCCN guidelines for bladder preservation (P<0.0001). Treatment at an HVF was associated with the improved OS for all patients (P=0.001) and for the subset of patients receiving NCCN-recommended RT doses (P=0.0081). Volume was an independent predictor of OS (P=0.002). CONCLUSIONS: Treatment at an HVF is associated with improved OS and greater guideline-concordant management among patients with MIBC.

Radical prostatectomy or radiotherapy for high- and very high-risk prostate cancer: a multidisciplinary prostate cancer clinic experience of patients eligible for either treatment.

OBJECTIVE: To compare radical prostatectomy (RP) vs radiotherapy (RT) with androgen-deprivation therapy (ADT) in the setting of patients with high-risk and very high-risk (VHR) prostate cancer who were deemed eligible for either therapy and made a treatment choice after consultation in a multidisciplinary prostate cancer clinic (MDPCC), and to compare the MDPCC patients' outcomes to a matched Surveillance, Epidemiology and End Results (SEER) cohort. PATIENTS AND METHODS: Prospectively collected, retrospective study comparing patients who underwent RP (231 patients) vs RT+ADT (73) from 2004 to 2013. Biochemical recurrence (BCR), local recurrence, distant metastasis failure, and overall survival (OS) were calculated for each treatment group overall and according to National Comprehensive Cancer Network risk strata. A propensity score matched comparison with a SEER cohort was performed for OS. RESULTS: There was no difference in local recurrence (hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.0-7.9; P = 0.06), distant metastasis failure (HR 2.5, 95% CI 0.8-7.8; P = 0.1) and OS (HR 1.35, 95% CI 0.4-4.8; P = 0.6) between patients undergoing RP vs RT+ADT. Patients treated via the MDPCC survived on average 16.9 months (95% CI 13.1-20.8) longer than those in the matched SEER cohort. CONCLUSIONS: Long-term outcomes appear similar amongst patients with high-risk and VHR prostate cancer deemed eligible for either RP or RT, and treated after consultation in a MDPCC. Outcomes of the MDPCC patients were superior to those of the matched SEER cohort.

Central Lymph Node Status has Significant Prognostic Value in the Clinically Node-Negative Tall-Cell Variant of Papillary Thyroid Cancer Regardless of T-Staging and Radioactive Iodine Administration: First Evidence From a Population-Based Study.

BACKGROUND: The prognostic value of central lymph node (CLN) status in papillary thyroid cancer (PTC) remains controversial. This study aimed to provide the first evidence on this issue for the aggressive tall-cell variant (TCV) subtype. METHODS: The study identified TCV patients from the Surveillance, Epidemiology, and End Results database. The Kaplan-Meier method, log-rank test, and multivariate Cox regression models were used for analysis. RESULTS: Of the 744 patients included, 404 were recorded as N0, which were pathologically or only clinically confirmed. Overall survival (OS) and cancer-specific survival (CSS) did not differ significantly between the N0 and pN1a patients (p > 0.05). To investigate the reason, the N0 patients were subdivided according to the number of examined lymph nodes (ELN). The patients with a N0 diagnosis confirmed by two or more ELNs (N0-e2+) showed significantly better outcomes than the pN1a patients and their N0 counterparts without ELN (N0-e0) (p < 0.05), whereas the N0-e0 and pN1a groups demonstrated comparable outcomes in both the log-rank and multivariate analyses (p > 0.05). Moreover, the subgroup analyses showed that even among the patients with early T-staging (T1-T2) or receipt of radioactive iodine (RAI) therapy, the N0-e0 patients still demonstrated compromised OS compared with the N0-e2+ group (p < 0.05). CONCLUSION: The cN0 patients without ELN (N0-e0) had outcomes similar to those of the pN1a patients, but showed a poorer OS than the N0-e2+ group regardless of T-staging and RAI administration, suggesting that occult CLN metastases might act as a negative prognosticator in cN0 TCV. Therefore, prophylactic central neck dissection might be considered for biopsy-proven cN0 TCV patients. Prospective studies are expected to further validate our conclusions.

Postoperative radioactive iodine-131 ablation is not necessary among patients with intermediate-risk differentiated thyroid carcinoma: a population-based study.

OBJECTIVE: To assess the effectiveness of radioactive iodine (RAI) ablation among patients with intermediate-risk differentiated thyroid cancer (DTC) following surgery. SUBJECTS AND METHODS: This population based study obtained information from the Surveillance, Epidemiology, and End Results (SEER) Program Research Data (1973-2013). National Cancer Institute, DCCPS, Surveillance Research Programme, Surveillance Systems Branch, released April 2016, based on the November 2015 submission. A total of 93,530 patients with primary thyroid cancer were identified in the SEER database during the period of 2004-2013 and focused on patients with DTC post-operatively treated or not treated with radioactive iodine (RAI). From these 9,127 patients were selected who had intermediate-risk DTC. A total of 8,601 patients were included in this study. For the overall population, the mean age of the population was 47.3 years and the majority were female (70.5%). RESULTS: Kaplan-Meier analysis found the mean overall survival time (os) for subjects with no radiation therapy which was 112.9 months and 114.9 months for those who received RAI ablation treatment (P<0.001). However, thyroid cancer-specific survival was not significantly different between treatment groups (117.7 vs. 118.0 months, log-rank test P=0.164). Overall survival and thyroid cancer-specific 1 year, 5 years, and 10-years survival rates were ≥89.8% and were similar between both treated groups. Multivariate analysis found age, gender, histologic type, and degree of lymph node metastases to be associated with OS, and age, gender, degree of lymph node metastasis and extra-thyroid tumor spread were independent factors for cancer-specific survival. In DTC patients with intermediate cancer risk multivariate analysis found that RAI was associated with a reduced risk of mortality compared with no radiation therapy (HR=0.710, 95% CI: 0.562-0.897, P=0.004) but no significant difference was seen in cancer-specific survival, either based on whole study population or on tumor size category. CONCLUSION: In DTC patients with intermediate cancer risk although postoperative RAI ablation following surgery showed a benefit in overall survival, no significant difference was seen in cancer-specific survival, either based on whole study population or on tumor size category.

Adjuvant Radiation Therapy Treatment Time Impacts Overall Survival in Gastric Cancer.

PURPOSE: Prolonged radiation therapy treatment time (RTT) is associated with worse survival in several tumor types. This study investigated whether delays during adjuvant radiation therapy impact overall survival (OS) in gastric cancer. METHODS AND MATERIALS: The National Cancer Data Base was queried for patients with resected gastric cancer who received adjuvant radiation therapy with National Comprehensive Cancer Network--recommended doses (45 or 50.4 Gy) between 1998 and 2006. RTT was classified as standard (45 Gy: 33-36 days, 50.4 Gy: 38-41 days) or prolonged (45 Gy: >36 days, 50.4 Gy: >41 days). Cox proportional hazards models evaluated the association between the following factors and OS: RTT, interval from surgery to radiation therapy initiation, interval from surgery to radiation therapy completion, radiation therapy dose, demographic/pathologic and operative factors, and other elements of adjuvant multimodality therapy. RESULTS: Of 1591 patients, RTT was delayed in 732 (46%). Factors associated with prolonged RTT were non-private health insurance (OR 1.3, P=.005) and treatment at non-academic facilities (OR 1.2, P=.045). Median OS and 5-year actuarial survival were significantly worse in patients with prolonged RTT compared with standard RTT (36 vs 51 months, P=.001; 39 vs 47%, P=.005); OS worsened with each cumulative week of delay (P<.0004). On multivariable analysis, prolonged RTT was associated with inferior OS (hazard ratio 1.2, P=.002); the intervals from surgery to radiation therapy initiation or completion were not. Prolonged RTT was particularly detrimental in patients with node positivity, inadequate nodal staging (<15 nodes examined), and those undergoing a cycle of chemotherapy before chemoradiation therapy. CONCLUSIONS: Delays during adjuvant radiation therapy appear to negatively impact survival in gastric cancer. Efforts to minimize cumulative interruptions to <7 days should be considered.

Pancreatic neuroendocrine tumors with involved surgical margins: prognostic factors and the role of adjuvant radiotherapy.

PURPOSE: Pancreatic neuroendocrine tumors (pNET) are rare neoplasms associated with poor outcomes without resection, and involved surgical margins are associated with a worse prognosis. The role of adjuvant radiotherapy (RT) in these patients has not been characterized. METHODS AND MATERIALS: We retrospectively evaluated 46 consecutive patients with positive or close (<1 mm) margins after pNET resection, treated from 1983 to 2010, 16 of whom received adjuvant RT. Median RT dose was 50.4 Gy in 1.8-Gy fractions; half the patients received concurrent chemotherapy with 5-fluorouracil or capecitabine. No patients received adjuvant chemotherapy. Cox multivariate analysis (MVA) was used to analyze factors associated with overall survival (OS). RESULTS: Median age at diagnosis was 56 years, and 52% of patients were female. Median tumor size was 38 mm, 57% of patients were node-positive, and 11% had a resected solitary liver metastasis. Patients who received RT were more likely to have larger tumors (median, 54 mm vs. 30 mm, respectively, p = 0.002) and node positivity (81% vs. 33%, respectively, p = 0.002) than those not receiving RT. Median follow-up was 39 months. Actuarial 5-year OS was 62% (95% confidence interval [CI], 41%-77%). In the group that did not receive RT, 3 patients (10%) experienced local recurrence (LR) and 5 patients (18%) developed new distant metastases, while in the RT group, 1 patient (6%) experienced LR and 5 patients (38%) developed distant metastases. Of all recurrences, 29% were LR. On MVA, male gender (adjusted hazard ratio [AHR] = 3.81; 95% CI, 1.21-11.92; p = 0.02) and increasing tumor size (AHR = 1.02; 95% CI, 1.01-1.04; p = 0.007) were associated with decreased OS. CONCLUSIONS: Long-term survival is common among patients with involved-margin pNET. Despite significantly worse pathologic features among patients receiving adjuvant RT, rates of LR between groups were similar, suggesting that RT might aid local control, and merits further evaluation.

Resected pancreatic neuroendocrine tumors: patterns of failure and disease-related outcomes with or without radiotherapy.

PURPOSE: Pancreatic neuroendocrine tumors (NET) are rare and have better disease-related outcomes compared with pancreatic adenocarcinoma. Surgical resection remains the standard of care, although many patients present with locally advanced or metastatic disease. Little is known regarding the use of radiotherapy in the prevention of local recurrence after resection. To better define the role of radiotherapy, we performed an analysis of resected patients at our institution. METHODS: Between 1994 and 2009, 33 patients with NET of the pancreatic head and neck underwent treatment with curative intent at Duke University Medical Center. Sixteen patients were treated with surgical resection alone while an additional 17 underwent resection with adjuvant or neoadjuvant radiation therapy, usually with concurrent fluoropyrimidine-based chemotherapy (CMT). Median radiation dose was 50.4 Gy and median follow-up 28 months. RESULTS: Thirteen patients (39%) experienced treatment failure. Eleven of the initial failures were distant, one was local only and one was local and distant. Two-year overall survival was 77% for all patients. Two-year local control for all patients was 87%: 85% for the CMT group and 90% for the surgery alone group (p = 0.38). Two-year distant metastasis-free survival was 56% for all patients: 46% and 69% for the CMT and surgery patients, respectively (p = 0.10). CONCLUSIONS: The primary mode of failure is distant which often results in mortality, with local failure occurring much less commonly. The role of radiotherapy in the adjuvant management of NET remains unclear.

Use of adjuvant 5-fluorouracil and radiation therapy after gastric cancer resection among the elderly and impact on survival.

PURPOSE: In randomized trials patients with resected nonmetastatic gastric cancer who received adjuvant chemotherapy and radiotherapy (chemoRT) had better survival than those who did not. We investigated the effectiveness of adjuvant chemoRT after gastric cancer resection in an elderly general population and its effects by stage. METHODS AND MATERIALS: We identified individuals in the Surveillance, Epidemiology, and End Results-Medicare database aged 65 years or older with Stage IB through Stage IV (M0) gastric cancer, from 1991 to 2002, who underwent gastric resection, using multivariate modeling to analyze predictors of chemoRT use and survival. RESULTS: Among 1,993 patients who received combined chemoRT or no adjuvant therapy after resection, having a later year of diagnosis, having a more advanced stage, being younger, being white, being married, and having fewer comorbidities were associated with combined treatment. Among 1,476 patients aged less than 85 years who survived more than 4 months, the 313 who received combined treatment had a lower mortality rate (hazard ratio, 0.83; 95% confidence interval, 0.71-0.98) than the 1,163 who received surgery alone. Adjuvant therapy significantly reduced the mortality rate for Stages III and IV (M0), trended toward improved survival for Stage II, and showed no benefit for Stage IB. We observed trends toward improved survival in all age categories except 80 to 85 years. CONCLUSIONS: The association of combined adjuvant chemoRT with improved survival in an overall analysis of Stage IB through Stage IV (M0) resected gastric cancer is consistent with clinical trial results and suggests that, in an elderly population, adjuvant chemoradiotherapy is effective. However, our observational data suggest that adjuvant treatment may not be effective for Stage IB cancer, is possibly appropriate for Stage II, and shows significant survival benefits for Stages III and IV (M0) for those aged less than 80 years.

Review of adjuvant radiochemotherapy for resected pancreatic cancer and results from Mayo Clinic for the 5th JUCTS symposium.

PURPOSE: To present an overview of Phase III trials in adjuvant therapy for pancreatic cancer and review outcomes at the Mayo Clinic after adjuvant radiochemotherapy (RT/CT) for resected pancreatic cancer. METHODS AND MATERIALS: A literature review and a retrospective review of 472 patients who underwent an R0 resection for T1-3N0-1M0 invasive carcinoma of the pancreas from 1975 to 2005 at the Mayo Clinic, Rochester, MN. Patients with metastatic or unresectable disease at the time of surgery, positive surgical margins, or indolent tumors and those treated with intraoperative radiotherapy were excluded from the analysis. Median radiotherapy dose was 50.4 Gy in 28 fractions, with 98% of patients receiving concurrent 5-fluorouracil- based chemotherapy. RESULTS: Median follow-up was 2.7 years. Median overall survival (OS) was 1.8 years. Median OS after adjuvant RT/CT was 2.1 vs. 1.6 years for surgery alone (p = 0.001). The 2-y OS was 50% vs. 39%, and 5-y was 28% vs. 17% for patients receiving RT/CT vs. surgery alone. Univariate and multivariate analysis revealed that adverse prognostic factors were positive lymph nodes (risk ratio [RR] 1.3, p < 0.001) and high histologic grade (RR 1.2, p < 0.001). T3 tumor status was found significant on univariate analysis only (RR 1.1, p = 0.07). CONCLUSIONS: Results from recent clinical trials support the use of adjuvant chemotherapy in resected pancreatic cancer. The role of radiochemotherapy in adjuvant treatment of pancreatic cancer remains a topic of debate. Results from the Mayo Clinic suggest improved outcomes after the administration of adjuvant radiochemotherapy after a complete resection of invasive pancreatic malignancies.

Randomized phase II trial of high-dose melatonin and radiation therapy for RPA class 2 patients with brain metastases (RTOG 0119).

PURPOSE: To determine if high-dose melatonin for Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) Class 2 patients with brain metastases improved survival over historical controls, and to determine if the time of day melatonin was given affected its toxicity or efficacy. RTOG 0119 was a phase II randomized trial for this group of patients. METHODS AND MATERIALS: RTOG RPA Class 2 patients with brain metastases were randomized to 20 mg of melatonin, given either in the morning (8-9 AM) or in the evening (8-9 PM). All patients received radiation therapy (30 Gy in 10 fractions) in the afternoon. Melatonin was continued until neurologic deterioration or death. The primary endpoint was overall survival time. Neurologic deterioration, as reflected by the Mini-Mental Status Examination, was also measured. RESULTS: Neither of the randomized groups had survival distributions that differed significantly from the historic controls of patients treated with whole-brain radiotherapy. The median survivals of the morning and evening melatonin treatments were 3.4 and 2.8 months, while the RTOG historical control survival was 4.1 months. CONCLUSIONS: High-dose melatonin did not show any beneficial effect in this group of patients.

Phase II study of consolidation chemotherapy after concurrent chemoradiation in cervical cancer: preliminary results.

PURPOSE: Our aim was to determine the efficacy of consolidation chemotherapy after concurrent chemoradiation (CCRT) using high-dose-rate brachytherapy in patients with locally advanced cervical carcinoma. METHODS AND MATERIALS: Patients with cervical carcinoma (FIGO stage IB2-IVA) were treated with external beam radiation therapy to the whole pelvis (50.4 Gy) and high-dose-rate brachytherapy (24 Gy to point A). Cisplatin 60 mg/m(2) (Day 1) and 5-fluorouracil 1000 mg/m(2) (Days 1-5) were given every 3 weeks starting concurrently with the radiation and followed by 3 more cycles of consolidation for a total of 6 cycles. RESULTS: Thirty patients (94%) received 3 more cycles of post-CCRT consolidation chemotherapy and were evaluable for the toxicity and efficacy of consolidation. The most common toxicities of Grade 2 or higher were nausea or vomiting (47%) and anemia (33%). Late complications of the rectum and bladder occurred in 13% and 6% of the patients, respectively. The clinical complete response rate was 87% (95% CI, 75%-99%). During a median follow-up of 27 months (range, 6-58 months), 5 patients (17%) had recurrence; the sites of failure were 3 (10%) inside the radiation field and 2 (7%) outside the radiation field. The estimated 3-year progression-free survival rate was 83% (95% CI, 67%-99%) and overall survival rate was 91% (95% CI, 79%-100%). CONCLUSIONS: Consolidation chemotherapy after CCRT is well tolerated and effective in patients with locally advanced cervical carcinoma. A prospective randomized trial to compare this treatment strategy with standard CCRT seems to be worthwhile.