IMRT sparing of normal tissues in locoregional treatment of breast cancer.

PURPOSE: This clinical study was designed to prospectively evaluate the acute and moderately-late cardiac and lung toxicities of intensity modulated radiation therapy delivered by helical tomotherapy (IMRT-HT) for locoregional breast radiation treatment including the internal mammary nodes (IMN). MATERIAL/METHODS: 30 patients with stage III breast cancers have been accrued in this study. All patients received adjuvant chemotherapy. Target volumes were defined as follows: the PTV included breast/chest wall, axillary level II, III, infra/supraclavicular, IM nodes CTVs plus 3 mm margins. The heart with subunits and the lungs were defined as critical organs. Dose to PTV was 50 Gy in 25 fractions. Acute toxicities were assessed every week and 2 weeks post treatment using the CTCAE v3.0.scale. The moderately-late toxicities were assessed clinically plus by cardiac myoview perfusion tests scheduled at baseline, 3 and 12-month follow-up, as well a CT chest at the 6 month follow-up. The data analysis is descriptive. RESULTS: All participants completed the 5-week course of radiation without interruption. Skin erythema was modest and mainly grade 1-2 between the 3rd and the 5th week of radiation treatment. Only 4/30 patients experienced grade 3 skin reactions, mostly seen 2 weeks post radiation. Only 5 patients demonstrated grade 1 or 2 dyspnea, but 3 of them already had symptoms pre-radiation treatment. With a median follow-up of 58 (24-76) months, there have been infrequent moderately-late side effects. Most were grade 1 and were sometimes present at the baseline assessment. Cardiac myoview tests done at baseline and 1-year follow-up for 15 out of 18 left sided breast cancers did not show any abnormalities related to radiation. The 6-month follow-up chest CT-scans done for 25 out of 30 patients showed minimal anterior lung fibrosis for 7 patients and were completely normal for the other 18. No locoregional recurrence has been recorded and the 5-year survival is 78% (95% CI: 70-97%). CONCLUSION: IMRT-HT for locoregional breast radiation is very well tolerated with minimal acute or moderately-late side effects. Cardiac and respiratory tests did not show any strong evidence of significant treatment related abnormalities. TRIAL REGISTRATION: clinicaltrials.gov: http://NCT00508352.

Interstitial brachytherapy in the management of persistent head and neck disease after definitive external beam radiation therapy.

PURPOSE: Persistent disease after definitive external beam radiation therapy for head and neck (H&N) malignancies negatively impacts survival. In this series, the effectiveness of low-dose-rate brachytherapy in the management of persistent H&N disease is explored. METHODS: All patients who received brachytherapy for persistent H&N disease between 1987 and 2002 were identified. Tumor and treatment characteristics and toxicities were recorded. Progression-free survival and overall survival estimates were generated. The influence of prognostic factors was determined. RESULTS: Twelve patients were analyzable. Brachytherapy was given curatively (n=4) in patients not amenable to surgery or in combination with surgical dissection to avoid carotid resection (n=8). Seven patients had disease progression with a median time to progression of 11 months (95% confidence interval: 0-22.9). The only negative prognostic factor was time to re-treatment (brachytherapy >4 months) after definitive treatment (p=0.003). Overall survival at 1 and 5 years was 50% and 21%, respectively. Toxicity was limited to one major complication (fistula) and five minor toxicities: low-grade radionecrosis (n=2), cellulitis (n=1), and wound dehiscence (n=2). CONCLUSION: In patients with persistent disease, brachytherapy is an appealing re-treatment alternative. When combined with neck dissection, brachytherapy yields less morbidity than the surgical alternative of carotid resection.

Brachytherapy in the retreatment of patients with new primary head and neck cancer.

OBJECTIVE: Re-treatment for cure of the Head and Neck (H&N) region is therapeutically challenging. In this review we explore the long-term results of Ir(192) low-dose-rate (LDR) brachytherapy in the select subgroup of patients treated for a new H&N malignancy. METHODS & MATERIAL: Thirteen patients received brachytherapy between 1987-2004 for a new primary H&N cancer, six of whom had been retreated previously. Brachytherapy was given as a monotherapy in eight patients and delivered adjuvantly in five patients. Three of the thirteen patients had advanced disease at the time of diagnosis. MAIN OUTCOME MEASURES: In addition to the known prognostic factors of stage and site, intent of brachytherapy and prior re-treatment status were assessed for their influence on local control (LC) and overall survival (OS). RESULTS: Local control differed by disease stage of the new primary tumor. With a median follow-up of 50 months, mean progression-free survival was 50.2 months [95%CI = 30.1-70.4] and the 2-year rate of LC was 58%. Adjuvant brachytherapy following surgery resulted in poor LC and OS due to advanced disease at diagnosis. Prior retreatment did not appear to affect LC or OS. OS at 2 and 5 years was 69% and 38%, respectively. There were no cases of grade III toxicity. CONCLUSIONS: LDR Brachytherapy for a new primary H&N cancer is a well-tolerated retreatment alternative that results in good local control. Our results suggest that the best chance for long-term survival remains in the routine follow-up and early diagnosis of the new H&N malignancy.

Interstitial low-dose-rate brachytherapy in the treatment of recurrent head and neck malignancies.

BACKGROUND: Recurrent head and neck malignancies are therapeutically challenging. Brachytherapy is a retreatment alternative to external-beam radiation therapy (EBRT). METHODS: Patients receiving brachytherapy during 1987-2004 for recurrent head and neck cancer were identified. Tumor and treatment characteristics and toxicities were recorded. Progression-free survival (PFS) and overall survival (OS) estimates were generated. The influence of prognostic factors was determined. RESULTS: Eighty-two patients were analyzable. Analysis was limited to patients who had brachytherapy for a first recurrence (n = 45). Brachytherapy (> or = 55 Gy) was a monotherapy in 22 of 45 patients. As part of their salvage brachytherapy treatments, 14 patients also underwent surgery; 3 patients also underwent EBRT; and 6 patients underwent surgery, EBRT, and brachytherapy. Retreatment morbidity included acute toxicity (n = 7) and late toxicity (n = 18). Median PFS was 15 months, and locoregional control rates at 1 and 2 years were 50% and 37%, respectively. Time to progression differed by site of the primary tumor (p = .10). Median OS was 16 months, and OS at 2 and 5 years was 33% and 11%, respectively. CONCLUSIONS: Brachytherapy for recurrent head and neck cancer has an acceptable toxicity profile and is viable alternative to EBRT. Further optimization of the best sites and doses for neck brachytherapy is required.

Penile brachytherapy: results for 49 patients.

PURPOSE: To report results for 49 men with squamous cell carcinoma (SCC) of the penis treated with primary penile interstitial brachytherapy at one of two institutions: the Ottawa Regional Cancer Center, Ottawa, and the Princess Margaret Hospital, Toronto, Ontario, Canada. METHODS AND MATERIALS: From September 1989 to September 2003, 49 men (mean age, 58 years; range, 22-93 years) had brachytherapy for penile SCC. Fifty-one percent of tumors were T1, 33% T2, and 8% T3; 4% were in situ and 4% Tx. Grade was well differentiated in 31%, moderate in 45%, and poor in 2%; grade was unspecified for 20%. One tumor was verrucous. All tumors in Toronto had pulsed dose rate (PDR) brachytherapy (n = 23), whereas those in Ottawa had either Iridium wire (n = 22) or seeds (n = 4). Four patients had a single plane implant with a plastic tube technique, and all others had a volume implant with predrilled acrylic templates and two or three parallel planes of needles (median, six needles). Mean needle spacing was 13.5 mm (range, 10-18 mm), mean dose rate was 65 cGy/h (range, 33-160 cGy/h), and mean duration was 98.8 h (range, 36-188 h). Dose rates for PDR brachytherapy were 50-61.2 cGy/h, with no correction in total dose, which was 60 Gy in all cases. RESULTS: Median follow-up was 33.4 months (range, 4-140 months). At 5 years, actuarial overall survival was 78.3% and cause-specific survival 90.0%. Four men died of penile cancer, and 6 died of other causes with no evidence of recurrence. The cumulative incidence rate for never having experienced any type of failure at 5 years was 64.4% and for local failure was 85.3%. All 5 patients with local failure were successfully salvaged by surgery; 2 other men required penectomy for necrosis. The soft tissue necrosis rate was 16% and the urethral stenosis rate 12%. Of 8 men with regional failure, 5 were salvaged by lymph node dissection with or without external radiation. All 4 men with distant failure died of disease. Of 49 men, 42 had an intact and tumor-free penis at last follow-up or death. The actuarial penile preservation rate at 5 years was 86.5%. CONCLUSIONS: Brachytherapy is an effective treatment for T1, T2, and selected T3 SCC of the penis. Close follow-up is mandatory because local failures and many regional failures can be salvaged by surgery.

Radiotherapy for localized prostate cancer: assessment of results by systematic biopsy and PSA.

This study attempted to determine the failure pattern after radiotherapy for localized prostate cancer using systematic biopsies and serum PSA in assessment of outcome. Between July 1987 and February 1993, 226 patients treated with radical external beam radiotherapy were followed prospectively with systematic transrectal ultrasound-guided biopsies and serum PSA. Four hundred and ten transrectal ultrasound-guided biopsies were performed with 4-7 samples (usually six) per session. Stage distribution was T1b: 32, T1c: 11, T2a: 45, T2b: 62, T3: 50, T4: 6. Median follow-up was 41 months. The rate of positive biopsies continued to decrease over time, reaching a nadir of 30.5% at 30 months post radiotherapy. Local failures have occurred in 17% (38/226) overall, or 13% of T1b, 0% of T1c, 13% of T2a, 20% of T2b and 21% of T3-4. Six additional patients (2.5%) have had biochemical failure and 34 (15%) have biopsy-only failure. Forty seven patients initially showing residual tumor on post radiotherapy biopsies (median time 18 months), demonstrated late tumor clearance, achieving negative biopsies at a median time of 28 months. Median nadir PSA in patients with no evidence of disease (NED) at last follow-up was 0.5 ng/mL, achieved at 24 months post radiotherapy. For patients with delayed tumor clearance, the median nadir PSA was 0.6 ng.mL at 27 months. For those with local failure it was 1.6 ng.mL at 16 months and for all failures, 1.8 ng/mL at 13 months. Systematic prostate biopsies show that tumor clearance after radiotherapy may take up to 30 months. Histologic tumor clearance parallels the fall in serum PSA. Serum PSA nadirs earlier and at a higher value in patients destined to fail.