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.

Treatment of squamous cell anal canal carcinoma (SCACC) with pulsed dose rate brachytherapy: a retrospective study.

BACKGROUND AND PURPOSE: To evaluate the results of pulsed dose rate brachytherapy (PDR) in SCACC. MATERIAL AND METHODS: From 1996 to 2002, 71 patients (pts) with SCACC were treated with PDR brachytherapy. The median age was 61.2 years (35-88), with a sex ratio of 1 M/6.5 F. The TNM classification was: 14 T1, 41 T2, 15 T3 and 1 T4, 52 N0, 13 N1, 3 N2 and 3 N3. All the pts were M0. Treatment started with external beam irradiation to the posterior pelvis (mean dose: 45.5 Gy). Forty-seven patients received chemotherapy (neoadjuvant/concomitant or both). After an interval of 2-6 weeks, PDR interstitial brachytherapy was performed. The mean dose was 17.8 Gy to the 85% reference isodose of the Paris system. RESULTS: Treatment was interrupted in only one pt. With a median follow-up of 28.5 months, 2-year actuarial overall survival was 90%. Fourteen relapses occurred (four distant, three regional, and seven local). Ten patients developed a grade III complication (Lent Soma scale) and two a grade IV complication (colostomy or abdominal perineal resection for necrosis). CONCLUSION: PDR appears to be an effective treatment for SCACC. It is capable of reproducing the results usually observed with continuous LDR.

Preoperative radiotherapy for rectal adenocarcinoma: Which are strong prognostic factors?

PURPOSE: This retrospective 12-year study evaluated the prognostic value of initial and postoperative staging of rectal tumors. METHODS AND MATERIALS: Between 1985 and 1996, 297 patients were treated with preoperative radiotherapy (39 Gy in 13 fractions) and surgery for Stage T2-T4N0-N1M0 rectal adenocarcinoma. Pretreatment staging included a clinical examination and endorectal ultrasonography (EUS) since 1988. Clinical staging was performed by digital rectal examination and rigid proctoscopy. EUS was performed in 236 patients. Postoperative staging was performed by examination of the pathologic specimen. RESULTS: The median follow-up was 49 months. The overall 5-year survival rate was 67%, with a local failure rate of 9%. The rate of sphincter preservation was 65%. The clinical examination findings were strong prognostic factor for both cT stage (p < 0.001) and cN stage (p < 0.006) but had poor specificity for cN stage (only 25 lymph nodes detected). In both univariate and multivariate analyses, EUS had a statistically significant prognostic value for uT (p < 0.014) but not for uN (p < 0.47) stage. In contrast, pT and pN stages were strong prognostic factors (p < 0.001 and p < 0.001, respectively). CONCLUSION: Pretreatment staging, including clinical examination and EUS, seemed accurate enough to present a high prognostic value for the T stage. EUS was insufficient to stage lymph node involvement. Owing to its lack of specificity, uN stage was not a reliable prognostic factor. An improvement in N staging is necessary and essential. Despite downstaging, postoperative staging remained a very strong prognostic factor for both T and N stages.

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.

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.

Adenoid cystic carcinoma of the nasopharynx: a case report and a discussion about prognostic factors and the role of local treatments.

Adenoid cystic carcinoma (ACC) is a rare epithelioid malignancy. It occurs most frequently in the salivary glands, while its localization in the nasopharynx is rare and few cases have been reported in the literature. We report the case of a 32-year-old woman presenting with ACC of the nasopharynx who was treated with surgery and adjuvant intensity-modulated radiation therapy (IMRT, total dose: 68 Gy) and concomitant chemotherapy (cisplatin 100 mg/m² on the first and 21st days of IMRT). During irradiation, the patient developed G1 dermatitis and G2 mucositis (RTOG). Clinical and instrumental reevaluation 17 months after the end of radiotherapy did not show any signs of relapse, and she did not show any sign of local mild-severe toxicity. Adjuvant radiotherapy after standard complete surgical resection seems to be effective and well tolerated and should be strongly considered in the multidisciplinary approach to this infrequent carcinoma.

Salvage radiotherapy after high-intensity focussed ultrasound for recurrent localised prostate cancer.

BACKGROUND: Radiotherapy is a treatment option in the case of local failure following treatment for localised prostate cancer with high-intensity focussed ultrasound (HIFU). OBJECTIVE: Our aim was to evaluate tolerance and oncologic control with salvage radiotherapy (SRT) after HIFU failure and to identify predictive factors of success. DESIGN, SETTING, AND PARTICIPANTS: From March 1995 to March 2008, all patients who presented with histologically proven persistent local disease following HIFU and were treated with curative intent SRT (with or without hormonal treatment) were included in this single-centre retrospective study. INTERVENTION: Patients underwent conformal radiotherapy. The median dose of conformal treatment was 72 Gy (65-78 Gy). MEASUREMENTS: The primary outcome measure was progression-free survival (PFS) defined as no biochemical relapse (three consecutive rises in prostate-specific antigen [PSA] with a velocity >0.4 ng/ml per year or PSA >1.5 ng/ml) and no additional treatment. Predictive factors of failure were examined in univariate and multivariate analyses. Adverse events in terms of urinary and digestive toxicity, urine incontinence, and erectile dysfunction (ED) were reported. RESULTS AND LIMITATIONS: The median (range) and mean (standard deviation) follow-up of the 100 patients analysed was 33 mo (5-164 mo) and 37.2 mo (23.6 mo), respectively. Eighty-three patients received SRT alone, and 17 received SRT and androgen-deprivation therapy. For the 83 patients treated with exclusive radiation therapy, PFS was 72.5% at 5 yr and 93%, 67%, and 55% for the low-, intermediate-, and high-risk groups, respectively. In the univariate analysis, PSA level prior to SRT, risk status, PSA nadir after SRT, PSA nadir after SRT >0.2 ng/ml, and time to achieve this nadir were all predictive of failure. In the multivariate analysis, PSA nadir post-SRT with a threshold at 0.2 ng/ml and time to achieve this nadir were the significant predictive factors of failure. Gastrointestinal toxicity was low; urinary toxicity grade < or =2 was 34.5%. Four were grade 3 (4.7%), one was grade 4 (1.2%), and one was grade 5 (1.2%). The incidence of severe ED (International Index of Erectile Dysfunction-5 score 5-10) was 14% pre-HIFU, and 51.9% and 82.3% pre- and post-SRT, respectively. Because our study was retrospective, results have to be interpreted cautiously. CONCLUSIONS: SRT provides satisfactory oncologic control after HIFU failure with little (or mild) additional toxicity. These results warrant further investigation.

GEC-ESTRO recommendations for brachytherapy for head and neck squamous cell carcinomas.

Both primary and recurrent squamous cell carcinoma of the head and neck are classic indications for brachytherapy. A high rate of local tumor control at the cost of limited morbidity can be achieved with brachytherapy through good patient selection, meticulous source implantation and careful treatment planning. However, no randomized trials have been performed, and there is scant evidence in the literature especially regarding practical clinical recommendations for brachytherapy for head and neck subsites. The Head and Neck Working Group of the European Brachytherapy Group (Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) therefore decided to formulate the present consensus recommendations for low-dose rate, pulsed-dose rate and high-dose rate brachytherapy. The use of brachytherapy in combination with external beam radiotherapy and/or surgery is also covered as well as the use of brachytherapy in previously irradiated patients. Given the paucity of evidence in the literature, these recommendations are mainly based on clinical experience accumulated by the members of the working group over several decades and the respective publications. The recommendations cover in a general part (1) patient selection, the pre-treatment work up and patient care, (2) treatment strategy, (3) target definition, (4) implant techniques, (5) dose and dose rate prescription, (6) treatment planning and reporting, (7) treatment monitoring (8) catheter removal, and (9) post-treatment patient care and follow-up. The recommendations are then specified for the classical brachytherapy tumor sites following an analogue more focussed structure (patient selection, implant technique, target definition, dose and dose rate prescription, results): lip, oral mucosa, mobile tongue, floor of mouth, oropharynx, nasopharynx, paranasal sinuses.

Prognostic factors of squamous cell carcinoma of the anal margin treated by radiotherapy: the Lyon experience.

BACKGROUND: To report our patient experience with squamous cell carcinoma of the anal margin and to evaluate the prognostic factors influencing outcome. MATERIALS AND METHODS: Between 1980 and 2001, 26 patients with anal margin squamous cell carcinoma were treated in Lyon-Sud: 7 T1, 14 T2, 4 T3, and 1 T4 with 20 N0, 3 N1, and 3 N2. The anal canal was invaded in five patients. Treatment consisted of definitive external irradiation in 14 patients and adjuvant irradiation (after a local excision) in 12 patients. External irradiation was combined with chemotherapy in seven patients, brachytherapy in four patients, and both brachytherapy and chemotherapy in one patient. RESULTS: The local control rate was initially 61.4%, and it was 80.8% after salvage treatment. The 5-year overall and specific survival rates were 71 and 88.3%, respectively. Three factors correlated with specific survival: cell differentiation (P=0.038) and T (P=0.001) and N category (P=0.0005). A salvage abdominoperineal resection was successfully employed in five of seven local recurrences. Four grade 3 and two grade 4 toxicities were observed. Sphincter preservation was possible in 66% of alive patients. CONCLUSION: Our results confirm the dominating place of definitive irradiation and radiochemotherapy in the treatment of anal margin squamous cell carcinoma. The indications for abdominoperineal resection must be limited to local relapse. The prognosis of squamous cell carcinoma is correlated to T and N staging and cell differentiation.