18F-choline PET/CT driven salvage radiotherapy in prostate cancer patients: up-date analysis with 5-year median follow-up.

PURPOSE: Salvage radiotherapy is generally considered as the standard treatment for biochemical relapse after surgery. Best results have been obtained with a PSA value < 0.5 ng/ml at relapse, while 60-66 Gy is deemed as standard total dose. Modern imaging, as dynamic-18F-choline PET/CT may identify site of recurrence, allowing dose escalation to a biological target volume. METHODS: Hundred and fifty patients showed a local relapse at dynamic-18F-choline PET/CT at time of biochemical recurrence. High-dose salvage radiotherapy was delivered up to total dose of 80 Gy to 18F-choline PET/CT positive area. Toxicity and relapse-free survival were recorded. RESULTS: Median PSA value at the beginning of salvage radiotherapy was 0.47 ng/ml (range 0.2-17.5 ng/ml). One-hundred and thirty nine patients (93%) completed salvage radiotherapy without interruptions. Acute gastrointestinal grade ≥ 2 toxicity was recorded in 13 patients (9%), acute genitourinary grade ≥ 2 toxicity in 2 patients (1.4%). One patient (0.7%) experienced late gastrointestinal grade 4 toxicity and 2 patients (1.4%) late acute genitourinary grade 3 toxicity. With a median follow-up of 63.5 months, 5 and 7-years relapse-free survival were 70% and 60.7%, respectively. CONCLUSION: With a median follow-up of 5 years the present study confirms that high-dose salvage radiotherapy to a biological target volume is feasible, with low rate of late toxicity and promising activity.

¹8F-choline positron emission tomography/computed tomography-driven high-dose salvage radiation therapy in patients with biochemical progression after radical prostatectomy: feasibility study in 60 patients.

PURPOSE: To retrospectively review data of a cohort of patients with biochemical progression after radical prostatectomy, treated according to a uniform institutional treatment policy, to evaluate toxicity and feasibility of high-dose salvage radiation therapy (80 Gy). METHODS AND MATERIALS: Data on 60 patients with biochemical progression after radical prostatectomy between January 2009 and September 2011 were reviewed. The median value of prostate-specific antigen before radiation therapy was 0.9 ng/mL. All patients at time of diagnosis of biochemical recurrence underwent dynamic (18)F-choline positron emission tomography/computed tomography (PET/CT), which revealed in all cases a local recurrence. High-dose salvage radiation therapy was delivered up to total dose of 80 Gy to 18F-choline PET/CT-positive area. Toxicity was recorded according to the Common Terminology Criteria for Adverse Events, version 3.0, scale. RESULTS: Treatment was generally well tolerated: 54 patients (90%) completed salvage radiation therapy without any interruption. Gastrointestinal grade ≥2 acute toxicity was recorded in 6 patients (10%), whereas no patient experienced a grade ≥2 genitourinary toxicity. No grade 4 acute toxicity events were recorded. Only 1 patient (1.7%) experienced a grade 2 gastrointestinal late toxicity. With a mean follow-up of 31.2 months, 46 of 60 patients (76.6%) were free of recurrence. The 3-year biochemical progression-free survival rate was 72.5%. CONCLUSIONS: At early follow-up, (18)F-choline PET/CT-driven high-dose salvage radiation therapy seems to be feasible and well tolerated, with a low rate of toxicity.

Design and evaluation of a methodology to perform personalized visual biofeedback for reducing respiratory amplitude in radiation treatment.

A methodology to perform personalized visual biofeedback aimed to the reduction of respiratory amplitude is here proposed. A custom-made software allows to adapt the biofeedback parameters to a patient's respiratory pattern by calculating a limiting range for respiratory amplitude obtained from data acquired during free breathing. The proposed methodology has been tested on ten healthy volunteers and on five lung cancer patients undergoing radiotherapy treatment. The protocol for volunteers consisted of 3 min of data acquisition during the subject's free breathing, 2 min of visual biofeedback within the limits, and 3 min of free breathing. The patients' free breathing was acquired in 3 min and the visual biofeedback performed during all the sessions of the radiotherapy treatment, i.e., an average of eight sessions and an average total treatment time of 2000 s each patient. All the volunteers and three patients of the five found the protocol comfortable. The settlement time needed for considering the limiting range stabilized during free breathing has been calculated as 120 +/- 10 s (p < 0.05). During visual biofeedback the baseline shift was removed and the average respiratory amplitude was reduced by about 40% for all the subjects. The variability of the breathing amplitude remained unaltered during biofeedback. Eight volunteers and three patients remained within the limiting range for more than 90% of the biofeedback period; all subjects remained within the limiting range for more than 80% of the biofeedback period. During the biofeedback period both groups, volunteers and patients, showed a significant increase in breathing frequency which was mostly doubled. Patients with shallow breathing performed comfortably the biofeedback.

Preoperative chemoradiation and intra-operative radiotherapy for pancreatic carcinoma.

AIMS AND BACKGROUND: In recent years, preoperative chemoradiation has received growing interest for the treatment of locally advanced pancreatic cancer. In an attempt to improve resectability and disease control, we used preoperative radiation therapy and concomitant 5-fluorouracil in a combined modality therapy protocol. The aim of the study was to evaluate definitive results in terms of toxicity, response and clinical outcome. MATERIAL AND METHODS: Twenty-eight patients with unresectable (cT4, 19 patients) or resectable (cT3, 9 patients) nonmetastatic pancreatic tumors received radiotherapy (39.6 Gy) plus 5-fluorouracil (continuous infusion, days 1-4 at 1000 mg/m(2)/day). After 4 weeks, patients were evaluated for surgical resection. In 9 resected patients, electron-beam intra-operative radiotherapy (10 Gy) was given before reconstruction. Thereafter, in resected patients, adjuvant chemotherapy was prescribed. RESULTS: During chemoradiation, 1 patient (3.6%) developed grade 3 acute gastrointestinal toxicity and 2 patients (7.1%) developed grade 3 hematological toxicity. Three of 19 patients with unresectable tumors had tumor downstaging (15.8%). Two patients showed partial response (response rate, 7.1%; 95% CI, 0.2-25.3) and 4 patients (14.3%) had minimal tumor response. Four patients (14.3%) showed progressive disease after chemoradiation. One postoperative death was recorded. The median survival time was 11.3 months (20.5 and 9.0 months in resected and unresected patients, respectively). Only one local failure was recorded in 8 patients resected with negative margins. CONCLUSIONS: Although the response rate is still low, our preliminary results suggest that preoperative 5-fluorouracil chemoradiation is well tolerated and may result in tumor downstaging. Delivery of intra-operative radiotherapy seems to be associated with a low rate of local recurrences.

Complete response after chemoradiation in ampullary carcinoma: a case report.

AIMS AND BACKGROUND: The case of a 70-year-old patient with resectable, poorly differentiated adenocarcinoma of the ampulla of Vater is presented. PATIENT AND METHODS: Due to intraoperative hemorrhagic complications, surgical resection was not feasible. The patient was treated with radiochemotherapy consisting of external beam radiotherapy (50.4 Gy; 1.8 Gy/fraction; 5 fractions/week) plus 5-FU (1000 mg/m2/day, continuous i.v. infusion, days 2-5, week 1 and 5 of radiotherapy) and mitomycin C (10 mg/m2 i.v., day 2, week 1 of radiotherapy). RESULTS: At five years' follow-up the patient was in good general condition, without any signs of disease according to CT scan, endoscopic retrograde cholangiopancreatography and tumor marker determination. Multiple random biopsies performed in the ampullary region were negative for tumor growth. CONCLUSIONS: In patients with ampullary carcinoma the use of concurrent chemoradiation should be considered, particularly when surgical resection is unfeasible due to medical contraindications or locally advanced disease.

Does downstaging predict improved outcome after preoperative chemoradiation for extraperitoneal locally advanced rectal cancer? A long-term analysis of 165 patients.

PURPOSE: To evaluate the impact of tumor response; tumor and nodal downstaging; and cTNM, yTNM (clinical stage after chemoradiation, based on preoperative imaging), and pTNM classifications on long-term outcome in patients with rectal cancer treated with preoperative 5-fluorouracil (5-FU)-based concurrent chemoradiation. METHODS AND MATERIALS: Between January 1990 and March 1998, 165 consecutive patients with locally advanced extraperitoneal cancer of the rectum were treated with preoperative chemoradiation. Four patients had a cT2 lesion (2.5%), 120 had a cT3 lesion (74.5%), and 41 had a cT4 lesion (23%). The nodal involvement at combined imaging was cN0 in 21%, cN1 in 41%, cN2 in 34%, and cN3 in 4%. Preoperative chemoradiation was delivered according to 1 of 3 schedules: (1) FUMIR-T3 (from 1990 to 1995) for patients with cT3N0-2 or cT2N1-2 rectal carcinoma (82 patients): 37.8 Gy (1.8 Gy/fraction) plus 5-FU, 1 g/m(2)/d on Days 1-4, continuous infusion, and mitomycin-C, 10 mg/m(2)/d on Day 1; (2) FUMIR-T4 (from 1990 to 1999) for patients with cT4N0-3 or cT3-4N3 rectal carcinoma (40 patients): 45 Gy (1.8 Gy/fraction) plus 5-FU, 1 g/m(2)/d on Days 1-4 and 29-32, continuous infusion, and mitomycin-C, 10 mg/m(2)/d on Days 1 and 29; and (3) PLAFUR-4 (from 1995 to 1998) for patients with cT3N0-2 or cT2N1-2 rectal carcinoma (42 patients): 50.4 Gy (1.8 Gy/fraction) plus 5-FU, 1 g/m(2)/d on Days 1-4 and 29-32, continuous infusion, and cisplatin, 60 mg/m(2)/d on Days 1 and 29. Four to five weeks after chemoradiation, patients were reevaluated for clinical response by imaging studies (CT scan, transrectal ultrasonography, barium enema, liver ultrasonography, chest X-rays) and restaged (yTNM). Surgery was performed 6-8 weeks after chemoradiation. Adjuvant chemotherapy (5-FU + l-folinic acid) was delivered to 26 patients in the FUMIR-T4 protocol group. Local control (LC), freedom from distant metastases (FDM), disease-free survival, and overall survival (OS) were evaluated according to the clinical response and cTNM, yTNM, and pTNM classification. The median follow-up was 67 months. RESULTS: The 5-year survival rate was 100% for cT2, 77% for cT3, and 62% for cT4 (p = 0.0497); after chemoradiation, it ranged between 81% and 91% for pT0-pT2 and dropped to 66% for pT3 and 47% for pT4 (p = 0.014). The 5-year local control rate was, at the first staging, 84% for cT3 and 72% for cT4; after chemoradiation, the pT stage correlated significantly with LC (p = 0.0012): 100% for pT0, 83% for pT1, 88% for pT2, 79% for pT3, and 46% for pT4. N stage was statistically significant in predicting FDM and OS at any staging step. A significant impact of tumor response, tumor downstaging, and nodal downstaging on LC, FDM, disease-free survival, and OS was also recorded. If the residual tumor, before surgery, had a tumor index <30 (i.e., width less than one-quarter of rectal circumference and length in its caudocranial axis < or =30 mm), the 5-year LC, FDM, disease-free survival, and OS rates were significantly higher at both the univariate and the multivariate analyses. The surgical procedure was tailored according to tumor downstaging, and thus the choice of sphincter-preserving surgery was based on the distance between the lower pole of the tumor and the anorectal ring "after" chemoradiation. In 36 patients with the lower pole of the lesion in the range of 0-30 mm from the anorectal ring, 16 patients (44%) underwent a sphincter-saving procedure. All clinical outcomes were similar compared with 20 patients with tumor located at the same rectum level who received an abdominoperineal resection. CONCLUSION: After preoperative chemoradiation, clinical response and tumor/nodal pathologic downstaging showed a close correlation with improved outcomes. The better 5-year survival and local control in pT0-2 patients regardless of their initial stage seems to confirm a heterogeneity in rectal cancer patients. The responder population showed a behavior similar to rectal cancer diagnosed at Stage cT1-2 and treated with conservative surgery alone. Additional studies aimed at improving local tumor response seem justified. Trials of sphincter-saving surgery after a major response are warranted.