Intraoperative Electron Radiation Therapy Combined with External Beam Radiation Therapy after Gross Total Resection in Extremity Soft Tissue Sarcoma: A European Pooled Analysis.

INTRODUCTION: We report a pooled analysis evaluating the combination of gross complete limb-sparing surgery, intraoperative electron radiation therapy (IOERT), and external beam radiation therapy (EBRT) in patients with extremity soft tissue sarcoma (STS). METHODS: Individual data of 259 patients (median follow-up 63 months) with extremity STS from three European expert centers were pooled. Median age was 55 years and median tumor size was 8 cm. Eighty percent of patients presented with primary disease, mainly located in the lower limb (81%). Union for International Cancer Control 7th edition stage at presentation was as follows: stage I: 9%; stage II: 47%; stage III: 39%; stage IV: 5%. Most patients showed high-grade lesions (91%), predominantly liposarcoma (31%). Median IOERT dose was 12 Gy, preceeded (17%) or followed (83%) by EBRT, with a median dose of 45 Gy. RESULTS: Surgery resulted in R0 resections in 71% of patients and R1 resections in 29% of patients. The 5-year local control (LC) rate was 86%, and significant factors in univariate analysis were disease status and resection margin. Only margin remained significant in multivariate analysis. The 5-year distant control rate was 69%, and significant factors in univariate analysis were histology, grading, resection margin, and metastases prior to/at IOERT. Only grading and metastases remained significant in multivariate analysis. Actuarial 5-year rates of freedom from treatment failure and OS were 61% and 78%, respectively. Significant factors for OS were grading and metastases prior to/at IOERT (univariate, multivariate). Limb preservation and good functional outcome were achieved in 95% and 81% of patients. CONCLUSIONS: Our pooled analysis confirmed prior reports of encouraging LC and survival, with excellent rates of preserved limb function with this treatment approach. Resection margin remained the most important factor for LC, while grading and metastases prior to/at IOERT mainly predicted survival.

Image-guided volumetric arc radiotherapy of pancreatic cancer with simultaneous integrated boost: Optimization strategies and dosimetric results.

PURPOSE: To introduce volumetric modulated arc therapy treatments (VMAT) with simultaneous integrated boost (SIB) for pancreatic cancer and describe dosimetric results on a large patient series. METHODS AND MATERIALS: 45 patients with pancreatic malignancies were treated with 18 MV single-arc VMAT. Image guidance was performed with daily online kilo-volt cone-beam computed tomography (CBCT). The conformity index (CI) and homogeneity index (HI) to the target volumes, PTV45Gy and PTV54Gy, and dose-volume indices to OARs from the QUANTEC task group were reported. The risk of clinical nephritis was evaluated using normal tissue complication probability (NTCP). Treatments were verified in-phantom with the Delta4 system. RESULTS: Average CI was 1.06 with 95% confidence intervals (95% CI) of 0.97-1.22 for PTV45Gy and 1.17 (0.66-1.61) for PTV54Gy. HI of PTV54Gy was 1.06 (1.04-1.10). OAR constraints were achieved in all patients, except for kidneys V12Gy of 48 (35.4-72.3)%. NTCP of the kidneys was 0.98 (0.6-1.7)%. Kidneys V12Gy and V20Gy were inversely related to PTV54Gy CI and maximum dose. All in-phantom tests had gamma pass rates exceeding 95% with global 3% dose difference and 3 mm distance to agreement. Patient shifts measured with CBCT had 95% CI of -0.8, +0.8 in the RL, -0.7, +0.8 in the SI, and -0.8, +0.7 cm in the AP directions. CONCLUSIONS: Dosimetric results of VMAT were excellent on PTVs and organs at risk. The kidneys represent the dose-limiting organ at risk for this technique. NTCP indicates that this technique is safe from radiation-induced side effects to the kidneys.

Patterns of radiotherapy practice for pancreatic cancer: Results of the Gastrointestinal Radiation Oncology Study Group multi-institutional survey.

No information is currently available regarding pancreatic cancer (PC) pattern of care in Italy. In the present study, a nationwide survey using a questionnaire was performed to enquire the local standards for PC diagnosis and radiotherapy treatment. Fifty-seven percent of 140 Italian centres completed questionnaire. The main causes of no radiotherapy indication were poor general condition (45%) and lack of guidelines (25%). Physicians (38%) employed neoadjuvant therapy in locally advanced PC patients, while in other centres (62%) adjuvant chemoradiation was administered. Adjuvant gemcitabine-based chemotherapy was selected as the treatment of choice by 59% of centres. Patients were treated mostly with doses of 50-54.9 Gy on the tumour (or bed) plus lymph nodes. A 3D-CRT technique was used in 81.2% of centres, while IMRT and IGRT were available in 61.2 and 48.7% of cases, respectively. Extensive variation exists with regard to patterns of care for PC in Italy. Nevertheless, cooperative studies emerging from this survey appeared beneficial.

Long-term outcome of patients with complete pathologic response after neoadjuvant chemoradiation for cT3 rectal cancer: implications for local excision surgical strategies.

BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) followed by radical surgery including total mesorectal excision (TME) is standard treatment in patients with locally advanced rectal cancer. Emerging data indicate that patients with complete pathologic response (ypCR) after CRT have favorable outcome, suggesting the possibility of less invasive surgical treatment. We analyzed long-term outcome of cT3 rectal cancer treated by neoadjuvant CRT in relation to ypCR and type of surgery. METHODS: The study population comprised 139 patients (93 men, 46 women; median age 62 years) with cT3N0-1M0 mid and distal rectal adenocarcinoma treated by CRT and surgery (110 TME and 29 local excision) at our institution between 1996 and 2008. At pathology, ypCR was defined as no residual cancer cells in the primary tumor. RESULTS: Tumors of 42 patients (30.2%) were classified as ypCR. After a median follow-up of 55.4 months, comparing patients with ypCR to patients with no ypCR, 5-year disease-specific survival was 95.8% versus 78.0% (P = 0.004), and 5-year disease-free survival was 90.1% vs. 64.0% (P = 0.004). In patients with ypCR, no statistically significant outcome difference was observed between TME and local excision. In patients treated by local excision, comparing patients with ypCR to patients with no ypCR, 5-year disease-free survival was 100% vs. 65.5% (P = 0.024), and 5-year local recurrence-free survival was 92.9% vs. 66.7% (P = 0.047). CONCLUSIONS: With retrospective analysis limitations, our data confirm favorable long-term outcome of cT3 rectal cancer with ypCR after CRT and warrant clinical trials exploring local excision surgical strategies.

Dietary habits and risk of pancreatic cancer: an Italian case-control study.

OBJECTIVE: To investigate the association between dietary habits and pancreatic cancer. METHODS: Between 1991 and 2008, we conducted a hospital-based case-control study in northern Italy. CASES: 326 patients (median age 63 years) with incident pancreatic cancer admitted to general hospitals in the areas of Milan and Pordenone, northern Italy. CONTROLS: 652 patients (median age 63 years) with acute non-neoplastic conditions admitted to the same hospital network of cases. Diet was assessed using a validated food frequency questionnaire. Conditional logistic regression was used to estimate odds ratios (OR) and the corresponding 95% confidence intervals (CI). RESULTS: Frequent meat consumption was associated to a twofold increased risk of pancreatic cancer (95% CI: 1.18-3.36); the risk was significant for meat cooked by boiling/stewing or broiling/roasting. Added table sugar (OR = 2.23; 95% CI: 1.34-3.71) and potatoes (OR = 1.79; 95% CI: 1.12-2.86) were related to pancreatic cancer. An inverse association emerged for non-citrus fruits (OR = 0.41; 95% CI: 0.24-0.69), cooked vegetables (OR = 0.57; 95% CI: 0.36-0.92), and, possibly, for pulses (OR = 0.59; 95% CI: 0.35-1.00). CONCLUSIONS: The present study supports an inverse association between fruits and vegetables and pancreatic cancer risk, and it confirms a direct relation with meat. The increased risk for table sugar suggests that insulin resistance may play a role in pancreatic carcinogenesis.

Infusional 5-fluorouracil and ZD1839 (Gefitinib-Iressa) in combination with preoperative radiotherapy in patients with locally advanced rectal cancer: a phase I and II Trial (1839IL/0092).

PURPOSE: To report the final data of a Phase I and II study (1839IL/0092) on the combination of an anti-epidermal growth factor receptor drug (gefitinib), infusional 5-fluorouracil, and preoperative radiotherapy in locally advanced, resectable rectal cancer. METHODS AND MATERIALS: Patients received 45 Gy in the posterior pelvis plus a boost of 5.4 Gy on the tumor and corresponding mesorectum. Infusional 5-fluorouracil (5-FU) and gefitinib (250 and 500 mg/day) were delivered during all radiotherapy course. An IORT boost of 10 Gy was allowed. The main endpoints of the study were to establish dose-limiting toxicity (DLT) and to evaluate the rate of pathologic response according to the tumor regression grade (TRG) Mandard score. RESULTS: A total of 41 patients were enrolled. The DLT was not reached in the 6 patients enrolled in the dose-escalation part of the study. Of the 33 patients in the Phase II, TRG 1 was recorded in 10 patients (30.3%) and TRG 2 in 7 patients (21.2 %); overall 17 of 33 patients (51.5%) had a favorable endpoint. Overall, Grade 3+ toxicity was recorded in 16 patients (41%); these included Grade 3+ gastrointestinal toxicity in 8 patients (20.5%), Grade 3+ skin toxicity in 6 (15.3%), and Grade 3+ genitourinary toxicity in 4 (10.2%). A dose reduction of gefitinib was necessary in 24 patients (61.5%). CONCLUSIONS: Gefitinib can be associated with 5-FU-based preoperative chemoradiation at the dose of 500 mg without any life-threatening toxicity and with a high pCR (30.3%). The relevant rate of Grade 3 gastrointestinal toxicity suggests that 250 mg would be more tolerable dose in a neaoadjuvant approach with radiotherapy and infusional 5-FU.

Neoadjuvant therapy of rectal cancer new treatment perspectives.

During the past two decades, significant advances have been made in the management of patients with rectal cancer. A number of clinical studies have demonstrated the efficacy of preoperative chemoradiation therapy with 5-fluorouracil (5-FU)-based regimens in decreasing local recurrences and improving survival and the likelihood of sphincter preservation. Although 5-FU has been the standard drug used in combination with radiation therapy for many years, new effective drugs including capecitabine, raltitrexed, irinotecan and oxaliplatin have been recently investigated in combination with radiation therapy in the preoperative setting. In addition, novel targeted biological agents including epidermal growth factor receptor inhibitors and vascular endothelial growth factor inhibitors have been shown to enhance the antitumor effect of both radiation and chemotherapy and are currently being explored in initial clinical trials. In the present review we summarize the results of adjuvant therapy. In addition, we will discuss the recently reported phase I-II trials with new drug plus radiation combinations in the preoperative treatment of patients with rectal cancer.

Combined modality treatment for locally advanced gastric cancer.

The positive results recently reported by the Intergroup 0116 Study with adjuvant chemoradiation have stimulated an increasing interest in the combined modality treatment of gastric cancer. The significant improvement in disease-free and overall survival reported in this study was related mainly to an improvement in local control rather than to a decrease in the incidence of metastatic disease. Therefore, new and potentially more effective chemotherapy regimens could be considered and the feasibility of their integration with radiation therapy needs to be explored to further improve the treatment in gastric cancer. Our experience with combined radiation therapy and 5-FU-with or without 5-FU based chemotherapy--in unresectable and in partially or radically resected gastric cancer is retrospectively reviewed. In addition, an initial prospective evaluation of the feasibility and toxicity of radiation and 5-FU following adjuvant chemotherapy with modern platinum containing regimens is reported. Our data and the current available experiences with investigational approaches in gastric cancer involving preoperative chemotherapy and intraoperative radiotherapy will be considered in exploring a new combined modality treatment program.