Role of brachytherapy in the treatment of cancers of the anal canal. Long-term follow-up and multivariate analysis of a large monocentric retrospective series.

BACKGROUND AND PURPOSE: There are few data on long-term clinical results and tolerance of brachytherapy in anal canal cancer. We present one of the largest retrospective analyses of anal canal cancers treated with external beam radiotherapy with/without (±) chemotherapy followed by a brachytherapy boost. MATERIALS AND METHODS: We performed a retrospective analysis of clinical results in terms of efficacy and toxicity. The impact of different clinical and therapeutic variables on these outcomes was studied. RESULTS: From May 1992 to December 2009, 209 patients received brachytherapy after external beam radiotherapy ± chemotherapy. Of these patients, 163 were stage II or stage IIIA (UICC 2002) and 58 were N1-3. According to age, ECOG performance status (PS), and comorbidities, patients received either radiotherapy alone (58/209) or radiochemotherapy (151/209). The median follow-up was 72.8 months. The 5- and 10-year local control rates were 78.6 and 73.9 %, respectively. Globally, severe acute and late G3-4 reactions (NCI-CTC scale v. 4.0) occurred in 11.2 and 6.3 % of patients, respectively. Univariate analysis showed the statistical impact of the pelvic treatment volume (p = 0.046) and of the total dose (p = 0.02) on the risk of severe acute and late toxicities, respectively. Only six patients required permanent colostomy because of severe late anorectal toxicities. CONCLUSION: After a long follow-up time, brachytherapy showed an acceptable toxicity profile and high local control rates in patients with anal canal cancer.

Paclitaxel is effective in relapsed head and neck squamous cell carcinoma: a retrospective study of 66 patients at a single institution.

The standard first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma is cisplatin-based chemotherapy, but taxanes can also be beneficial after progression or in patients not eligible for cisplatin. The objective of this retrospective study was to evaluate paclitaxel in this population. We reviewed 66 patients who were treated with paclitaxel at a single institution (Lyon, France) between January 2003 and November 2008. Paclitaxel was administered as first, second or more line of treatment; alone or in combination with carboplatin or cetuximab; every 3 weeks (175 mg/m(2)) or weekly (80 mg/m(2)). Forty-six (70%) patients received paclitaxel as first-line therapy after relapse and 26 (39%) patients as monotherapy. The objective response rate was 30% [95% confidence interval (CI): 20-43%]; 37% (95% CI: 23-52%) in the first line after relapse, and 20% (95% CI: 4-48%) in the second line. Rates were 19% (95% CI: 7-39%) after monotherapy and 36% (95% CI: 20-55%) after combination with carboplatin. Two of the six patients receiving cetuximab had a partial response. The overall survival of all patients was 7.2 months (95% CI: 5.2-8.8). Paclitaxel can be used in symptomatic patients. Although no improvement of overall survival can be expected, paclitaxel treatment is safe and achieves interesting response rates.

Exclusive brachytherapy for T1 and T2 squamous cell carcinomas of the velotonsillar area: results in 44 patients.

PURPOSE: To evaluate the role of interstitial brachytherapy as an exclusive radiotherapy modality for primary T1-T2 squamous cell carcinomas (SCC) of the velotonsillar area. METHODS AND MATERIALS: Between 1992 and 2000, 44 patients with T1-T2 SCC of the tonsil (n = 36) and soft palate (n = 8) were treated to the primary with brachytherapy alone (37 patients) or after a limited resection (7 patients). Eight patients had prior external beam radiation therapy (EBRT) for previous head-and-neck carcinoma. Nineteen patients had initial neck dissection. The mean brachytherapy dose was 58.7 Gy, and the mean reference dose rate and Ir-192 linear activity were 58.2 cGy/h and 1.51 mCi/cm respectively. RESULTS: With a 75-month median follow-up, 1 patient recurred locally. Isolated nodal relapses occurred in 4 patients, none of whom had initial neck dissection, and salvage therapy was successful in 2. Five-year overall and progression-free survival rates were 76% and 68%, respectively. Full-course radiation therapy was possible in 7 of 12 patients who developed a second primary head-and-neck carcinoma. Late toxicity was limited to 6 mild soft-tissue necroses, and was significantly associated with previous surgery to the primary and high linear activity. CONCLUSIONS: Exclusive brachytherapy for T1-T2 velotonsillar carcinomas is safe and effective, and permits definitive reirradiation for a second head-and-neck cancer. Initial neck dissection should be performed for optimal selection for exclusive brachytherapy.

Radiotherapy potentiation with weekly cisplatin compared to standard every 3 weeks cisplatin chemotherapy for locoregionally advanced head and neck squamous cell carcinoma.

BACKGROUND: Despite its toxicity, cisplatin every 3 weeks (q3w) is the standard potentiation of chemo-radiotherapy for head and neck squamous cell carcinoma. This study aimed to determine whether weekly cisplatin (q1w) could be a safe and effective alternative. PATIENTS AND METHODS: Two hundred and sixty-two patients with head and neck squamous cell carcinoma, irradiated in our institution with cisplatin (q1w or q3w) between January 2004 and December 2008, were retrospectively included. Overall survival (OS) and progression-free survival (PFS) were evaluated. Survival distributions were estimated by Kaplan-Meier method and compared using the log-rank test. Prognostic effect of chemo-radiotherapy was explored using Cox model. RESULTS: A total of 165 and 97 patients received q1w and q3w cisplatin, respectively. Median age, stage at diagnosis, alcohol consumption, intensity-modulated radiation therapy use, median weight, and renal failure before radiotherapy were significantly different, showing lower risk in the q3w group. Q3w cisplatin was found to be more toxic in terms of weight loss, renal failure, worse chemotherapy plan completion, and grade 3/4 mucositis and dermatitis, with more patients requiring analgesics, secondary hospitalization, and radiotherapy interruption (≥3 days), and patients affected by long-term toxicities. With a median follow-up of 73 months (95% confidence interval [CI] [68.9-76.2]), OS was found to be significantly better with q3w (5 years OS: 62.3%; 95% CI [51.6-71.3]) than with q1w cisplatin (5 years OS: 52.6%; 95% CI [44.5-60.0]) (log-rank P=0.0146). More number of patients treated according to the q1w schedule experienced a recurrence: 47.3% vs 30.9% (P=0.009). Thus, the PFS for q3w schedule was found to be globally better (5 years PFS: 55.8%; 95% CI [45.0-65.3]) than for q1w schedule (5 years PFS: 43.6%; 95% CI [35.9-51.0]) (log-rank P=0.0161). However, both multivariate analyses, OS and PFS, produce no significant hazard ratio for chemo-radiotherapy modality once adjusted on unbalanced covariates according to the descriptive analysis. CONCLUSION: Though q1w seemed to be safer than q3w according to the descriptive analysis, multivariate analyses failed to conclude about its efficiency. Therefore, we conclude that the q3w schedule should remain the standard and prospective comparisons are needed.

Role of brachytherapy in treatment of epidermoid carcinomas of the vallecula after conservative supraglottic laryngectomy followed by irradiation.

PURPOSE: To evaluate survival and functional results of the treatment of carcinomas of the vallecula using surgery, irradiation, and interstitial brachytherapy. METHODS AND MATERIALS: Between 1990 and 1998, 36 patients with squamous cell carcinoma of the vallecula were treated with horizontal supraglottic functional laryngectomy, external beam radiotherapy (median dose 54 Gy), and additional interstitial brachytherapy (median dose 16 Gy). Results were compared with a previous series of 22 patients treated without brachytherapy. RESULTS: The median follow-up was 44 months. The 5-year actuarial overall survival rate was 61.3%. The 5-year specific survival rate was 86%, with 2 local failures (local control rate 94.4%) and 4 isolated distant metastases. Ten patients developed a second primary. The overall survival was 34% for 22 patients previously treated without brachytherapy. Severe toxicities occurred in 9 patients: death (related to larynx edema or inhalation, n = 1), soft tissue necrosis (n = 1), aspiration pneumonia (n = 1), mandibular necrosis (n = 2), pharyngocutaneous fistula (n = 2), and laryngeal edema (n = 2). All the patients fed orally with no definitive gastrostomy or tracheotomy. CONCLUSION: Additional brachytherapy for vallecula carcinoma seems to improve locoregional control and overall survival dramatically. Functional results were also excellent. To our knowledge, this original therapeutic schedule has never been previously described.

Three-dimensional conformal radiotherapy for paranasal sinus carcinoma: clinical results for 25 patients.

PURPOSE: To assess local control, survival, and clinical and dosimetric prognostic factors in 25 patients with locally advanced maxillary or ethmoid sinus carcinoma treated by three-dimensional conformal radiotherapy (RT). MATERIALS AND METHODS: Surgery was performed in 22 patients and was macroscopically complete in 16. Seven patients received chemotherapy (concomitant with RT in four). The following quality indexes were defined for the 95% and 90% isodoses: tumor conformity index, normal tissue conformity index, and global conformity index. RESULTS: The median radiation dose to the planned treatment volume was 63 Gy, with a minimal dose of 60 Gy, except in 2 patients whose cancer progressed during RT. The maximal doses tolerated by the structures involved in vision were respected, except for tumors that involved the optic nerve. After a median follow-up of 25 months, 14 local tumor recurrences developed. The major prognostic factors were central nervous system involvement by disease and the presence of nonresectable tumors. The radiation dose and tumor conformity index value were not significant prognostic indicators. Two patients died of acute infectious toxicity, and two developed late ipsilateral ocular toxicity. CONCLUSIONS: Improving local control remains the main challenge in RT for paranasal tumors.

Impact of dosimetric parameters on local control for patients treated with three-dimensional pulsed dose-rate brachytherapy for cervical cancer.

PURPOSE: To investigate the impact of dose-volume histograms parameters on local control of three-dimensional (3D) image-based pulsed dose-rate brachytherapy (BT). METHODS AND MATERIALS: Within a French multicentric prospective study, the data of the 110 patients treated for cervical cancer with external beam radiotherapy followed by 3D image-based and optimized pulsed dose-rate BT were analyzed. Delineation procedures were performed on magnetic resonance imaging in a minority of cases and on CT for the majority of cases, adapted from the Gynaecological Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology recommendations. Optimization procedure was left to the discretion of the treating center. RESULTS: At 2 years, local control rate reached 78%. Dose to Point A, total reference air kerma, and intermediate-risk clinical target volume (IR-CTV) V60 were predictive factors for local control (p = 0.001, p = 0.001, and p = 0.013, respectively). Patients with IR-CTV V60 <75% had a relative risk of local recurrence of 3.8 (95% confidence interval, 1.4-11.1). There was no correlation found between the high-risk clinical target volume dosimetric parameters and local control. CONCLUSIONS: This multicentric study has shown that 3D image-based BT provides a high local control rate for cervical cancer patients. The V60 for IR-CTV was identified as an important predictive factor for local control.

Radiochemotherapy and brachytherapy could be the standard treatment for anal canal cancer in elderly patients? A retrospective single-centre analysis.

Goal To retrospectively analyse all our elderly patients (>70 years old) treated with radiotherapy ± chemotherapy (RT ± CT) followed by brachytherapy (BRT) for anal canal cancer. Background Studies on clinical outcomes and toxicities of the standard treatments for anal canal cancers in elderly patients are rare and data are not homogeneous, so a standard of care cannot be defined for these patients. Study A retrospective analysis of efficacy and safety of RT ± CT followed by BRT has been performed. The impact of the modified Charlson Index and of other different clinical and therapeutic variables on these outcomes has been also studied. Results Seventy-six elderly patients with a histological diagnosis of anal canal cancer and with a median age of 76 years (range 70-88) were treated with a curative goal. Patients received radiotherapy alone (37/76, "RT group") or radiochemotherapy (39/76, "RT-CT group"). All patients underwent a BRT boost. Five-year local control, overall survival, disease-specific survival, nodal progression-free survival and metastasis-free survival rates were 75.8, 75.8, 82.8. 87.8 and 89.0 %, respectively. Globally, the incidence of acute and late Grade 3-4 toxicities was 14.5 and 6.6 %, respectively. Only 2 patients received surgery because of severe ano-rectal toxicities. Any relationship between the modified Charlson Index and all the considered clinical outcomes was found. Conclusions Curative RT ± CT + BRT showed an acceptable toxicity profile and a good efficacy also in elderly anal canal cancer patients and should be considered as an important therapeutic option also for these patients.

Permanent 125I-seed prostate brachytherapy: early prostate specific antigen value as a predictor of PSA bounce occurrence.

PURPOSE: To evaluate predictive factors for PSA bounce after 125I permanent seed prostate brachytherapy and identify criteria that distinguish between benign bounces and biochemical relapses. MATERIALS AND METHODS: Men treated with exclusive permanent 125I seed brachytherapy from November 1999, with at least a 36 months follow-up were included. Bounce was defined as an increase ≥ 0.2 ng/ml above the nadir, followed by a spontaneous return to the nadir. Biochemical failure (BF) was defined using the criteria of the Phoenix conference: nadir +2 ng/ml. RESULTS: 198 men were included. After a median follow-up of 63.9 months, 21 patients experienced a BF, and 35.9% had at least one bounce which occurred after a median period of 17 months after implantation (4-50). Bounce amplitude was 0.6 ng/ml (0.2-5.1), and duration was 13.6 months (4.0-44.9). In 12.5%, bounce magnitude exceeded the threshold defining BF. Age at the time of treatment and high PSA level assessed at 6 weeks were significantly correlated with bounce but not with BF. Bounce patients had a higher BF free survival than the others (100% versus 92%, p = 0,007). In case of PSA increase, PSA doubling time and velocity were not significantly different between bounce and BF patients. Bounces occurred significantly earlier than relapses and than nadir + 0.2 ng/ml in BF patients (17 vs 27.8 months, p < 0.0001). CONCLUSION: High PSA value assessed 6 weeks after brachytherapy and young age were significantly associated to a higher risk of bounces but not to BF. Long delays between brachytherapy and PSA increase are more indicative of BF.

Inverted papilloma with associated carcinoma of the nasal cavity and paranasal sinuses: treatment outcomes.

CONCLUSIONS: Degenerated inverted papilloma is a rare, aggressive, and lethal disease. To avoid missing the target, it is absolutely necessary to consider the microscopic extension even in cases of complete exeresis and to irradiate the whole of the adjacent sinuses. A dose increase may lead to better locoregional control. OBJECTIVE: To evaluate overall survival and progression-free survival of external radiotherapy in the management of nasal cavity and paranasal sinus inverted papilloma with associated carcinoma. METHODS: Clinical data from 11 patients treated by surgery followed by external radiotherapy (three-dimensional conformational radiotherapy until 2007 then intensity-modulated radiation therapy) for degenerated inverted papilloma in the Léon Bérard Cancer Centre between 1985 and 2009 were retrospectively analyzed. RESULTS: Five patients (45%) had a local recurrence and died from their recurrence. Three had a premature recurrence, just before or during radiotherapy. We could not determine the prognostic factors for overall survival and progression-free survival.

A new, simple maxillary-sparing tongue depressor for external mandibular radiotherapy: a case report.

BACKGROUND: In external radiotherapy, the use of leaded intraoral devices to shield adjacent tissues is well described, but stabilization of the mandible is often realized with standard bite blocks, which do not allow a good stabilization of the mandible. METHODS AND RESULTS: A 40-year-old patient presenting with a local recurrence of a tumor of the floor of the mouth underwent external radiotherapy. To shield the maxilla during mandibular irradiation and to ensure mandible and tongue immobility during external radiotherapy, a custom-made device was realized. The apparatus consists of a polymethylmethacrylate resin plate and 2 wedges. Only 2 steps are needed. CONCLUSION: The realization is simple and cheap, the apparatus is comfortable, and modifications are easy. It can be used in all patients, except in patients with totally mandibular edentulous with severe bone resorption.

Long-term survival of 106 stage III ovarian cancer patients with minimal residual disease after second-look laparotomy and consolidation radiotherapy.

OBJECTIVE: Attempts to increase survival in stage III ovarian cancer patients with minimal residual disease at second-look laparotomy have included consolidation radiotherapy. We present long-term survival of 106 consecutive patients treated between 1983 and 1993 in 4 French institutions for stage III ovarian adenocarcinoma with first-look debulking, cisplatin-based chemotherapy, second-look surgery with a residual disease <1 cm and consolidation radiotherapy. METHODS: Median age was 52 years. Residual disease after first look surgery was <1 cm for 40.5% of patients. Median number of chemotherapy cycles was 6 (range 4-12). Residual disease <1 cm at second-look laparotomy was observed in 79% of the patients, with 33% of patients in complete histologic remission. Residual disease <1 cm was obtained in all patients after tumor excision during second-look surgery. Radiation was performed using a linear accelerator with a whole abdomen dose of 22.5 Gy, an additional 22 Gy pelvic boost for 71 patients, and an additional 12 Gy lombo-aortic boost for 33 patients. RESULTS: Median follow-up was 14 years. Radiation was stopped for acute toxicity in 11 patients. Long-term toxicities included radiation enteritis in 21 patients with 9 patients requiring surgery for bowel obstruction. Four deaths were related to enteritis complications. Overall survival at 5 and 10 years was respectively 53% and 36%. CONCLUSION: This sequential treatment with final consolidation abdominopelvic radiotherapy is an effective treatment for a selected group of stage III ovarian cancer patients with a high intestinal toxicity incidence.