Chemoradiation in Unresectable Biliary Tract Cancer: A Systematic Review

Aim: To present a systematic review on efficacy and toxicity of modern concurrent chemoradiation (CCRT) in unresectable biliary tract cancers (BTC). Methods: A systematic review of literature published within the last ten years (1 January 2007-31 December 2017), based on PRISMA methodology and using PubMed electronic database was conducted. Only articles reporting patients’ outcome in terms of toxicity and/or overall survival (OS) or progression-free survival (PFS) after CCRT, with or without other treatments, were analyzed. Only studies of patients with diagnosis of unresectable BTC, including intrahepatic, extrahepatic, and gallbladder neoplasm were considered. Results: Six eligible studies were included reporting data on 195 patients. Median follow-up ranged between 9.4 and 27.7 months (median: 16 months). Four studies were prospective phase II trials and 2 had a retrospective design. Different external beam radiotherapy (EBRT) techniques and chemotherapy (CT) schedules were used while only in one study a brachytherapy boost was delivered. Grade ≥ 3 acute toxicity (hematological or gastrointestinal) ranged between 0.0 and 55.6% (median: 37.0%). One study reported 30.0% gastrointestinal grade ≥ 2 late toxicity. PFS ranged between 6.8 and 10.5 months (median: 7.5 months) in 5 studies. OS ranged between 9.6 and 13.5 months (median: 13 months) in 5 studies. Conclusion: CCRT remains a reasonable treatment option for locally advanced BTC, providing results comparable with the ones of standard CT, particularly in terms of OS. Considering the progressive advance of modern EBRT techniques, further improvement of these results can be expected. Therefore, clinical trials based on advanced radiotherapy techniques and new integrations of CCRT with systemic treatments are warranted

Analysis of intraprostatic failures in patients treated with hormonal therapy and radiotherapy: implications for conformal therapy planning

PURPOSE: Conformal therapy of prostate cancer is based on high-dose irradiation to the entire prostate gland. The aim of this study was to analyze the pattern of intraprostatic recurrence in patients undergoing external beam radiotherapy (EBRT) at a dose of 65-70 Gy to evaluate whether conventional radiotherapy doses are adequate to control microscopic disease outside the primary tumor and therefore whether high-dose irradiation can be exclusively focused on the macroscopic disease. METHODS AND MATERIALS: The clinical and radiologic reports of 118 patients with prostate cancer undergoing EBRT (64.8-70.2 Gy) combined with hormonal therapy were evaluated. In all patients, before and after therapy, the size and site of the primary neoplasm within the prostate were assessed by clinical examination and imaging studies. RESULTS: With a median follow-up of 45 months (range 14-119), the 5-year actuarial local control rate was 83.9%. Twelve patients had an intraprostatic recurrence, with the appearance of a new nodule (in 5 patients with a complete response after therapy) or increased nodular size compared with the minimal size (in the 7 other patients). In all patients, on the basis of a semiquantitative evaluation of the site of recurrence, this was shown to originate within the initial tumor volume. CONCLUSION: The results of this analysis seem to confirm some histologic findings observed in patients undergoing prostatectomy for local recurrence after radiotherapy that suggest that local recurrence usually originates in the primary tumor rather than in focal prostatic intraepithelial neoplasia. This observation might justify the application of conformal therapy procedures aimed at identifying the gross tumor volume, in the phase of boost, exclusively with the primary tumor

5-fluorouracil-based chemoradiation in unresectable pancreatic carcinoma: Phase I-II dose-escalation study

Purpose: A Phase I-II dose-escalation study was performed to evaluate the possible impact of the dose on response, toxicity, pain relief, and outcome in patients with unresectable pancreatic carcinoma. Methods and Materials: A total of 50 patients entered the study. The external beam radiotherapy (RT) dose was 39.6 Gy in the first 15 patients, 50.4 Gy in the next 15 patients, and 59.4 Gy in the remaining 20 patients, at five 1.8-Gy fractions weekly. During external beam RT, patients received concurrent continuous infusion of 5-fluorouracil (1000 mg/m(2) on Days 1-4 and 21-24). Patients were evaluated for toxic reactions, local disease control, survival, and pain relief. Results: No treatment-related deaths occurred from acute toxicity. Four patients required a temporary treatment interruption because of acute hematologic (2 patients) or GI (2 patients) toxicity, not correlated with the delivered RT dose. Three patients (6%) developed late toxicity (duodenal ulcer in 2 and duodenal stenosis in 1). All patients who developed late toxicity had received a dose of 59.4 Gy. At univariate analysis, only the RT dose correlated significantly with the incidence of late toxicity (at 2 years, 39.6-50.4 Gy resulted in 0% and 59.4 Gy resulted in 58.2%; p = 0.023). At multivariate analysis, the RT dose also showed a trend with the incidence of late side effects (p = 0.052). Overall, 6 patients had a partial response (12%) and 44 (88%) had no change. The overall response rate was 8.0% (95% confidence interval, 1.5-20.5%). The rate of response was not different in the three groups. In-field locoregional disease progression was seen in 7 patients (14.0%). Distant relapse was documented in 34 patients (68.0%). None of analyzed variables, in particular, the RT dose delivered, showed a statistically significant correlation with objective response, local control, incidence of metastasis, disease-free survival, or overall incidence of pain symptoms after therapy. The whole group median survival was 9 months. The actuarial survival rate at 1, 2, and 3 years was 31.3%, 2.8%, and 0.0%, respectively. None of analyzed parameters correlated significantly with survival at univariate or multivariate analysis. Conclusion: In a Phase I-II study, the association of high RT doses with the incidence of severe toxicity in the treatment of unresectable pancreatic carcinoma was confirmed. Furthermore, this dose-escalation study did not document a clearcut correlation, using 5-fluorouracil-based chemoradiation, between the radiation dose and clinical outcome. (C) 2004 Elsevier Inc

Postoperative hypofractionated radiation therapy in prostate Carcinoma: A systematic review

A systematic review on toxicity, local control (LC), overall survival (OS), and biochemical relapse-free survival (bRFS) after postoperative hypofractionated radiotherapy (HFRT) on prostate cancer (PCa) was performed

Capecitabine based postoperative accelerated chemoradiation of pancreatic carcinoma. A dose-escalation study

The objective of this study was to evaluate the safety of escalating up to 55 Gy within five weeks, the dose of external beam radiotherapy to the previous tumor site concurrently with a fixed daily dose of capecitabine, in patients with resected pancreatic cancer. MATERIAL AND METHODS: Patients with resected pancreatic carcinoma were eligible for this study. Capecitabine was administered at a daily dose of 1600 mg/m (2). Regional lymph nodes received a total radiation dose of 45 Gy with 1.8 Gy per fractions. The starting radiation dose to the tumor bed was 50.0 Gy (2.0 Gy/fraction, 25 fractions). Escalation was achieved up to a total dose of 55.0 Gy by increasing the fraction size by 0.2 Gy (2.2 Gy/fraction), while keeping the duration of radiotherapy to five weeks (25 fractions). A concomitant boost technique was used. Dose limiting toxicity (DLT) was defined as any grade>3 hematologic toxicity, grade>2 liver, renal, neurologic, gastrointestinal, or skin toxicity, by RTOG criteria, or any toxicity producing prolonged (> 10 days) radiotherapy interruption. RESULTS AND DISCUSSION: Twelve patients entered the study (median age: 64 years). In the first cohort (six patients), no patient experienced DLT. Similarly in the second cohort, no DLT occurred. All 12 patients completed the planned regimen of therapy. Nine patients experienced grade 1-2 nausea and/or vomiting. Grade 2 hematological toxicity occurred in four patients. The results of our study indicate that a total radiation dose up to 55.0 Gy/5 weeks can be safely administered to the tumor bed, concurrently with capecitabine (1600 mg/m (2)) in patients with resected pancreatic carcinoma

Postoperative intensity-modulated radiotherapy with simultaneous integrated boost in prostate cancer: A dose-escalation trial

OBJECTIVES:: To determine the recommended phase II dose of postoperative accelerated intensity modulated radiotherapy (IMRT) for prostate cancer. MATERIAL AND METHODS:: Step and shoot IMRT with simultaneous integrated boost (SIB) was delivered in 25 fractions over 5 weeks to patients with high risk resected prostate adenocarcinoma (stage pT3-4 and/or positive surgical margins). Pelvic nodes received 45 Gy at 1.8 Gy/fraction; dose escalation was performed only to the prostate bed (planned dose escalation: 56.8 Gy at 2.27 Gy/fraction, 59.7 Gy at 2.39 Gy/fraction, 61.25 Gy at 2.45 Gy/fraction, 62.5 Gy at 2.5 Gy/fraction). Dose-limiting toxicity (DLT) was any grade ≥ 3 acute toxicity (RTOG score). RESULTS:: Twenty-five patients were treated: 7 patients at the 56.75 Gy dose level, 6 patients at each subsequent dose level. Pathologic stages were: pT2c: 2; pT3a: 11; pT3b: 12; pN0: 22; pN1: 3; R0: 7; R1: 18. Median follow-up time was 19 months (range: 6-36 months). No patient experienced DLT. Grade 1-2 acute rectal and urologic toxicity was common (17 and 22 patients, respectively). CONCLUSIONS:: The recommended dose was 62.5 Gy in 2.5 Gy/fraction. Postoperative hypofractionated IMRT SIB for prostate cancer seemed to be well tolerated and could be tested in phase II studies

Early proctoscopy is a surrogate endpoint of late rectal toxicity in prostate cancer treated with radiotherapy

Purpose: To predict the grade and incidence of late clinical rectal toxicity through short-term (1 year) mucosal alterations. Methods and Materials: Patients with prostate adenocarcinoma treated with curative or adjuvant radiotherapy underwent proctoscopy a year after the course of radiotherapy. Mucosal changes were classified by the Vienna Rectoscopy Score (VRS). Late toxicity data were analyzed according to the Kaplan-Meier method. Comparison between prognosis groups was performed by log-rank analysis. Results: After a median follow-up time of 45 months (range, 18-99), the 3-year incidence of grade ≥2 rectal late toxicity according to the criteria of the European Organization for Research and Treatment of Cancer and the Radiation Therapy Oncology Group was 24%, with all patients (24/24; 100%) experiencing rectal bleeding. The occurrence of grade ≥2 clinical rectal late toxicity was higher in patients with grade ≥2 (32% vs. 15 %, p = 0.02) or grade ≥3 VRS telangiectasia (47% vs. 17%, p ≤ 0.01) and an overall VRS score of ≥2 (31% vs. 16 %, p = 0.04) or ≥3 (48% vs. 17%, p = 0.01) at the 1-year proctoscopy. Conclusions: Early proctoscopy (1 year) predicts late rectal bleeding and therefore can be used as a surrogate endpoint for late rectal toxicity in studies aimed at reducing this frequent complication

Impact of age and co-morbidities in patients with newly diagnosed glioblastoma: a pooled data analysis of three prospective mono-institutional phase II studies.

To analyse the impact of age and co-morbidities on compliance and outcomes in GBM patients enrolled in three prospective phase II trials. GBM patients ( 6518 years) were treated with radiotherapy (60 Gy) or enrolled in a Fractionated Stereotactic Conformal-Radiotherapy Phase II trial (69.4 Gy). Concomitant and adjuvant chemotherapy with Temozolomide (TMZ) was administered. Charlson Index Co-morbidity (CCI) was used to assess co-morbidity. Toxicity was evaluated according to RTOG score. Survival analysis was performed by the Kaplan-Maier. Influence of age and co-morbidity was evaluated using log-rank test. From 2001 to 2008, 146 patients were enrolled: 56 (38.4 %) aged over 65 and 90 under 65. CCI 651 was observed in 41 % of elderly and 22 % of young group. Patients' compliance was 97.9 % for radio-chemotherapy. Acute toxicity was mild with no difference between the groups. Global median progression-free survival (PFS) and overall survival (OS) were 12 and 18 months, respectively. Age, surgery and radiation dose correlated with survival (p = 0.01, p = 0.04 and p = 0.03). CCI 642 did not show any influence on OS. Our data show that elderly with a good performance status and few co-morbidity may be treated as younger patients; moreover, age confirms a negative impact on survival while CCI 642 did not correlated with OS