Radiotherapy with Intensity-Modulated (IMRT) Techniques in the Treatment of Anal Carcinoma (RAINSTORM): A Multicenter Study on Behalf of AIRO (Italian Association of Radiotherapy and Clinical Oncology) Gastrointestinal Study Group.

A multi-institutional retrospective study was conducted to evaluate the pattern of care and clinical outcomes of anal cancer patients treated with intensity-modulated radiotherapy (IMRT) techniques. In a cohort of 987 patients, the clinical complete response (CR) rate (beyond 6 months) was 90.6%. The 3-year local control (LC) rate was 85.8% (95% CI: 84.4-87.2), and the 3-year colostomy-free survival (CFS) rate was 77.9% (95% CI: 76.1-79.8). Three-year progression-free survival (PFS) and overall survival (OS) rates were 80.2% and 88.1% (95% CI: 78.8-89.4) (95% CI: 78.5-81.9), respectively. Histological grade 3 and nodal involvement were associated with lower CR (p = 0.030 and p = 0.004, respectively). A statistically significant association was found between advanced stage and nodal involvement, and LC, CFS, PFS, OS and event-free survival (EFS). Overall treatment time (OTT) ≥45 days showed a trend for a lower PFS (p = 0.050) and was significantly associated with lower EFS (p = 0.030) and histological grade 3 with a lower LC (p = 0.025). No statistically significant association was found between total dose, dose/fraction and/or boost modality and clinical outcomes. This analysis reports excellent clinical results and a mild toxicity profile, confirming IMRT techniques as standard of care for the curative treatment of anal cancer patients. Lymph node involvement and histological grade have been confirmed as the most important negative prognostic factors.

Time to surgery and pathologic complete response after neoadjuvant chemoradiation in rectal cancer: A population study on 2094 patients.

BACKGROUND: To retrospectively evaluate the difference in terms of pathologic complete response (pCR) according to time elapsed between chemoradiation (CRT) and total mesorectal excision (TME) on a large unselected real-life dataset of locally advanced rectal cancer (LARC) patients. METHODS: A multicentre retrospective cohort study of LARC patients from 21 Italian Radiotherapy Institutions was performed. Patients were stratified into 3 different time intervals from CRT. The 1st group included 300 patients who underwent TME within 6 weeks, the 2nd 1598 patients (TME within 7-12 weeks) and the 3rd 196 patients (TME within 13 or more weeks after CRT), respectively. RESULTS: Data on 2094 LARC patients treated between 1997 and 2016 were considered suitable for analysis. Overall, 578 patients had stage II while 1516 had stage III histological proven invasive rectal adenocarcinoma. A CRT schedule of one agent (N = 1585) or 2-drugs (N = 509) was administered. Overall, pCR was 22.3% (N = 468 patients). The proportion of patients achieving pCR with respect to time interval was, as follows: 12.6% (1st group), 23% (2nd group) and 31.1% (3rd group) (p < 0.001), respectively. The pCR relative risk comparison of 2nd to 1st group was 1.8, while 3rd to 2nd group was 1.3. Moreover, between the 3rd and 1st group, a pCR relative risk of 2.4 (p < 0.01) was noted. At univariate analysis, clinical stage III (p < 0.001), radiotherapy dose >5040 cGy (p = 0.002) and longer interval (p < 0.001) were significantly correlated to pCR. The positive impact of interval (p < 0.001) was confirmed at multivariate analysis as the only correlated factor. CONCLUSION: We confirmed on a population-level that lengthening the interval (>13 weeks) from CRT to surgery improves the pathological response (pCR and pathologic partial response; pPR) in comparison to historic data. Furthermore, radiotherapy dose >5040 cGy and two drugs chemotherapy correlated with pPR rate.

No benefit of adjuvant Fluorouracil Leucovorin chemotherapy after neoadjuvant chemoradiotherapy in locally advanced cancer of the rectum (LARC): Long term results of a randomized trial (I-CNR-RT).

BACKGROUND AND PURPOSE: To evaluate the effect of adjuvant chemotherapy (ACT) in locally advanced rectal cancer (LARC) after neoadjuvant chemoradiation (NACT-RT). The study was funded by the Italian National Research Council (CNR). METHODS: From September 1992 to January 2001, 655 patients with LARC (clinically T3-4, any N) treated with NACT-RT and surgery, were randomized in two arms: follow-up (Arm A) or 6 cycles of ACT with 5 fluorouracil (5FU)-Folinic Acid (Arm B). NACT-RT consisted of 45Gy/28/ff concurrent with 5FU (350mg/sqm) and Folinic Acid (20mg/sqm) on days 1-5 and 29-33; surgery was performed after 4-6weeks. Median follow up was 63·7months. Primary end point was overall survival (OS). RESULTS: 634/655 patients were evaluable (Arm A 310, Arm B 324); 92·5% of Arm A and 91% of Arm B patients received the preoperative treatment as in the protocol; 294 patients of Arm A (94·8%) and 296 of Arm B (91·3%) underwent a radical resection; complete pathologic response and overall downstaging rates did not show any significant difference in the two arms. 83/297 (28%) patients in Arm B, never started ACT. Five year OS and DFS did not show any significant difference in the two treatment arms. Distant metastases occurred in 62 patients (21%) in Arm A and in 58 (19·6%) in Arm B. CONCLUSIONS: In patients with LARC treated with NACT-RT, the addition of ACT did not improve 5year OS and DFS and had no impact on the distant metastasis rate.

Adjuvant whole pelvic radiotherapy in 43 patients with uterine serous cancer: outcome and patterns of failure.

AIMS AND BACKGROUND: Uterine serous cancer is associated with a poor outcome and poses a therapeutic challenge. We retrospectively evaluated the experience of the Radiotherapy Department of the University of Florence. METHODS: Forty-three patients with stage I-III uterine serous cancer underwent surgery with (18 patients, group 1) or without complete surgical staging (25 patients, group 2) followed by adjuvant whole pelvic radiotherapy alone or combined with vaginal brachytherapy (in 35 and 8 cases, respectively). The median dose delivered with whole pelvic radiotherapy was 50 Gy (range, 45-56) and for brachytherapy was 20 Gy (range, 20-30). RESULTS: Actuarial overall survival and disease-free survival rates at 5 years were 62.5% and 61%, respectively. Local failure was observed in 17 patients (39.5%) and distant metastasis in 10 (23.2%). Nine patients had both local failure and distant metastasis, which had developed concurrently in 7 cases. Isolated abdominal failure occurred in 4 cases (9.3%). Local relapse was noted in 22.2% of patients in group 1 compared to 52% in group 2. A trend towards a better 5-year overall survival (67.2% vs 58%), disease-free survival (63% vs 59%) and local control (70% vs 59%) was observed in group 1 than group 2, although the difference between the two groups failed to reach statistical significance. CONCLUSIONS: Given the patterns of failure of patients with uterine serous cancer, adjuvant whole pelvic radiotherapy may be a reasonable approach, although novel integrated strategies are needed because the results achieved remain disappointing. Adjuvant whole pelvic radiotherapy might improve overall survival, disease-free survival and local control in complete surgically staged patients, but further investigations are required.

Postoperative radiotherapy in stage I/II endometrial cancer: retrospective analysis of 883 patients treated at the University of Florence.

INTRODUCTION: The efficacy of postoperative radiotherapy (RT) in the treatment of early-stage endometrial carcinoma (EC) is still under debate. This study was aimed to review the outcome and adverse effects in patients treated for EC with postoperative RT at a single center. METHODS: A total of 883 patients with pathological stages I to II EC were retrospectively analyzed. Surgery consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy, or vaginal hysteroannessiectomy in 532 patients (60.2%) with pelvic lymphadenectomy in 351 patients (39.8%). Seven hundred forty-seven patients (84.6%) underwent whole pelvic RT (WPRT) and 136 (15.4%) combined WPRT and vaginal brachytherapy (BT) boost. RESULTS: At a median follow-up of 9 years (range, 1.2-27.6 years), we observed 10.6% disease relapse. Forty-seven patients experienced local recurrence (LR), and 38 patients experienced distant metastases (DMs). At univariate analysis, age at diagnosis (P < 0.0001), stage (P < 0.04), and histological subtype (P < 0.0001) resulted in significant prognostic factors. At multivariate analysis, histotype emerged as an independent relapse predictor (P = 0.0001). Acute WPRT-related toxicity was mild; diarrhea was the most common adverse effect (19.8%). We recorded long-term adverse effects in 7.8% of the patients. CONCLUSIONS: Our study showed that patients with early-stage EC have a good outcome in overall survival and disease-free survival. In our experience, standard surgery (including hysterectomy and bilateral salpingo-oophorectomy followed by WPRT with or without BT) showed an acceptable toxicity profile.

Non-pegylated liposomal doxorubicin in combination with cyclophosphamide or docetaxel as first-line therapy in metastatic breast cancer: a retrospective analysis.

AIMS AND BACKGROUND: Anthracyclines such as doxorubicin play a central role in the management of advanced breast cancer. Unfortunately, the clinical benefits of anthracyclines are limited by cardiotoxicity that can lead to the development of potentially fatal congestive heart failure. In order to limit anthracycline-related cardiotoxicity, liposomal formulations of doxorubicin have been developed. This retrospective analysis evaluated the experience obtained with non-pegylated liposomal doxorubicin as first-line therapy in 34 patients with metastatic breast cancer. METHODS: Patients received non-pegylated liposomal doxorubicin in combination with either cyclophosphamide (n = 14) or docetaxel (n = 20) for up to eight cycles, and efficacy and safety were assessed according to standard criteria. RESULTS: The overall response rate was 71%. The median progression-free survival was 8 months in patients receiving non-pegylated liposomal doxorubicin plus cyclophosphamide and 13.8 months in those receiving non-pegylated liposomal doxorubicin plus docetaxel (P = 0.2). The most commonly observed toxicities were grade 1-2 leucopenia, alopecia, nausea and vomiting; no grade 3-4 toxicities were observed. Overall, three patients (9%) experienced grade 1 cardiac toxicity. CONCLUSIONS: Our results support the use of non-pegylated liposomal doxorubicin as an alternative to conventional doxorubicin formulations in combination regimens for the first-line therapy of metastatic breast cancer.

Alternating intravenous and oral vinorelbine plus epirubicin with pegfilgrastim as neoadjuvant treatment of locally advanced breast cancer.

In order to downstage locally advanced breast cancer, neoadjuvant chemotherapy consisting of intravenous vinorelbine 25 mg/m plus epirubicin 75 mg/m given on day 1 and oral vinorelbine 60 mg/m on day 8 was administered every 3 weeks for four courses. On day 2, all patients received a single subcutaneous injection of pegfilgrastim (6 mg). From March 2004 to June 2005, 22 patients were enrolled. Patients characteristics were: median age, 53 years (range: 39-70 years); postmenopausal, 7/22; clinical TNM stage, T2 (n=14), T3 (n=8), N0 (n=17) and N1 (n=5). The median number of courses was four (range: two to six courses) with full dose intensity. National Cancer Institute grade 3 haematological toxicities observed were neutropenia in 9% of patients, anaemia in 13% of patients and thrombocytopenia in 9% of patients; no toxicity grade 4 occurred. Two patients (9%) registered grade 2 polyneuropathy; no cardiac failure was observed. Conservative surgery was performed in 14 patients (63%). All patients were evaluable for response: complete pathological response was documented in three patients (13.6%); three patients (13.6%) obtained more than 75% of tumour size reduction; 11 other patients (50%) had 50% of tumour size reduction; stable disease was observed in five patients (22.7%). The present findings indicate that vinorelbine in combination with epirubicin is an effective and safe treatment in locally advanced breast cancer: this regimen obtained more than 50% of tumour size reduction in 77% of patients; the use of pegfilgrastim allowed full dose intensity. Oral vinorelbine on day 8 offers greater convenience to the patient by reducing the need for intravenous injection and the time spent in hospital.

Comparison of different external beam treatment techniques to deliver high-dose irradiation to local recurrent rectal carcinoma.

AIMS AND BACKGROUND: Treatment of local-regional recurrent rectal carcinoma is a challenging problem, and local control may be dose dependent; doses should probably exceed 60 Gy. Our aim was to verify the possibility to deliver 66 Gy to the target, but less than 35 Gy to the small bowel, comparing different 3D irradiation techniques, in a selected group of patients. METHODS: Five patients with local recurrent rectal carcinoma were selected as representative of different presentations of the disease. Gross tumor volume and clinical target volume were defined [by RS]. Tumors ranged between 182 and 540 cc, and small bowel volumes between 748 and 1050 cc. A three-field technique, coplanar multiple fields, noncoplanar fields and a proton beam were compared using dose volume histograms. A positive result was scored when > or = 90% of the target received the prescribed dose with no more than 5% of the small bowel receiving more than 35 Gy. Doses were escalated in steps of 2 Gy from 60 to 66 Gy. RESULTS: The number of plans fitting the constraints were 7/19, 11/19, 18/19 for doses of 66 Gy, 64 Gy and 62 Gy, respectively. The stage of the tumor did not seem to correlate with the possibility to homogeneously cover the target with the prescribed dose. CONCLUSIONS: Simple coplanar and complex coplanar techniques (up to six fields), positioning the patient in a prone position with dislocation of the bowel, seem to be the best solutions to treat almost all of the patients with doses of 64 Gy. Where higher doses are concerned, it is not possible to suggest a "standard" solution. More personalized techniques have to be tested to define the best option.