Antoine Ramade

Salvage brachytherapy of posterior pharyngeal wall squamous cell carcinoma in a previously irradiated area

PURPOSE Brachytherapy performed in patients with posterior pharyngeal wall carcinoma in a previously irradiated area is evaluated in terms of local control, survival, and complications. METHODS AND MATERIALS Between January 1982 and July 1993, 14 patients were treated with interstitial low dose rate brachytherapy alone for posterior pharyngeal wall squamous cell carcinoma in a previously irradiated area (local recurrences in five cases and second tumors in nine cases). Tumor size ranged from 1 to 4 cm. No patient had a macroscopic nodal involvement or metastase at the time of diagnosis. Median dose delivered was 55 Gy (39 to 60 Gy). RESULTS Thirteen patients were assessed for local control. Twelve of them achieved complete macroscopic response within 2 months after brachytherapy. Local relapse occurred in five patients, from 5 to 29 months after brachytherapy. One patient developed distant metastatis without loco-regional relapse. Disease free survival was 69, 59, and 37% at 1, 2, and 5 years, respectively; overall survival was 78, 50, and 21% at 1, 2, and 5 years, respectively. Three patients were still alive without recurrence (8, 8, and 10 years after treatment). We did not observe any severe acute or delayed toxicity. CONCLUSION Based on these results, interstitial brachytherapy should be considered as a potentially curative treatment for selected patients with posterior pharyngeal wall squamous cell carcinoma in a previously irradiated area. There are no reports in the literature on this subject.

Paclitaxel and cetuximab combination efficiency after the failure of a platinum-based chemotherapy in recurrent/metastatic head and neck squamous cell carcinoma.

The addition of cetuximab (CTX) to the combination of cisplatin and 5-fluorouracil increases the overall survival (OS) in recurrent/metastatic head and neck squamous cell carcinoma. Only a few patients are eligible for this treatment because of its toxicity. The combination of CTX and paclitaxel (TXL) could be included in sequential treatment strategies. Patients were treated with CTX (400/250 mg/m2) and TXL (60–80 mg/m2) weekly until disease progression or unacceptable toxicity. Efficacy and safety outcomes were determined retrospectively. A total of 42 patients were included in this analysis. The overall response rate was 38% [95% confidence interval (CI); 23–53%]. The disease control rate with TXL and CTX combination was 74%. Seven (17%) patients progressed before the first evaluation. The median progression-free survival was 3.9 months [95% CI; 3.1–4.7 months] and the median OS was 7.6 months [95% CI; 5.3–9.9 months]. Neurotoxicity and skin rash were the most frequent grade≥2 toxicities, reported in 17 and 12% of patients, respectively. Previous chemotherapy seems to be associated with a lower response rate and progression-free survival but not with the OS. The combination of CTX and TXL was an active and well-tolerated treatment in this series of patients with a poor prognosis and who were mostly symptomatic.

A RETROSPECTIVE, MULTICENTER STUDY OF THE TOLERANCE OF INDUCTION CHEMOTHERAPY WITH DOCETAXEL, CISPLATIN, AND 5-FLUOROURACIL FOLLOWED BY RADIOTHERAPY WITH CONCOMITANT CETUXIMAB IN 46 CASES OF SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK

PURPOSE To investigate, in a multicenter study, the tolerance of induction chemotherapy (ICT) and external radiotherapy (ERT) with concomitant cetuximab in the treatment of patients with squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS Clinical data from 46 patients with Stage III or IV nonmetastatic SCCHN who received docetaxel, cisplatin, and 5-fluorouracil as ICT, followed by ERT with concomitant cetuximab, were retrospectively analyzed. Clinical safety (weight, allergy, mucositis, and dermatitis) and paraclinical safety (levels of hemoglobin, polynuclear neutrophils, and creatinine clearance) were studied. The primary objective was the proportion of patients who completed the protocol. RESULTS The percentage of patients completing ICT was 73.9%, ERT 93.5%, and cetuximab 69.6%. Induction chemotherapy was better tolerated than that previously reported. The rates of temporary suspensions of radiation (39.1%, mean duration of 13 days) and hospitalization (26.1%) during ERT with concomitant cetuximab were high. Weight loss during treatment (21.4% of patients lost >10% of their body weight), radiodermatitis, and radiomucositis were the main causes of temporary suspension of treatment, although Grade 4 dermatitis was not experienced. There were no allergic reactions to cetuximab. CONCLUSION The completed protocol rate for SCCHN patients receiving ICT and ERT with concomitant cetuximab is high and the toxicity acceptable. Future improvements to protocol will be possible through early action and systematic implementation of nutritional support coupled with antibiotic treatment upon the first signs of radiodermatitis. These data could be useful for prospective studies on the safety and efficacy of this protocol.

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.

Inflammatory pseudotumor of the neck: A long-term result without surgical approach

a a fi t p nflammatory pseudotumor is a rare benign lesion, also alled plasma cell granuloma, inflammatory myofibroistiocytic proliferation, xanthomatous pseudotumor, nd plasma cell histiocytoma complex. Although the lung is the best known and most comon site, the inflammatory pseudotumor occurs in dierse extrapulmonary locations. This lesion has been escribed in most organs: mediastinum, heart, stomach, esentery, ileum, rectum, spleen, liver, genitourinary ract, pelvis and retroperitoneum, kidney, esophagus, ancreas, blood vessels. In the head and neck, inflamatory pseudotumors are unusual and have been decribed in the mouth, oropharynx, nasopharynx, paraharyngeal space, paranasal sinuses, pterygomaxillary pace, major salivary glands, larynx, trachea, thyroid, acrimal gland, orbit, central nervous system, menines, and temporal bone. The surgical treatment of inflammatory pseudotuor appears to be curative. The medical treatment is oorly documented and is not well established. In some ases, corticosteroids were used when the surgical reatment was too aggressive. The follow-up, however, as been sparse. We report to our knowledge the first case of inflamatory pseudotumor originating in the neck, successully treated with corticosteroids with a long-term folow-up of 5 years.

Transoral minimally invasive robotic surgery for carcinoma of the pharynx and the larynx: a new approach.

Partial laryngectomy is an old but well-accepted surgical treatment for selected carcinomas of the larynx. Actually, the transcervical approach remains the most popular even if the transoral laser approach is useful in some cases. Transoral robotic surgery is a new promising surgical procedure in head and neck oncology as an alternative to conventional surgery with decreased morbidity. The aim of this study is a description of the state of the art by a review of the literature. We emphasize limits and future prospects on this topic with a special focus on dependability.

Neoadjuvant TPF in locally advanced head and neck cancer can be followed by radiotherapy combined with cisplatin or cetuximab: a study of 157 patients.

Neoadjuvant TPF (docetaxel, cisplatin, 5-fluorouracil), followed by radiotherapy or chemoradiotherapy with weekly carboplatin, increases overall survival and organ preservation. We assessed whether TPF could be used in routine practice and whether radiotherapy potentiated with cisplatin or cetuximab was feasible and could increase survival. We retrospectively reviewed 157 patients with advanced head and neck squamous cell carcinoma treated with TPF in four French institutions between May 2005 and March 2009. After induction, operable patients had undergone surgery and were irradiated, and potentiated in some cases with cetuximab or cisplatin. Most patients (79%) had been treated with organ preservation strategies. The two most common sites were the hypopharynx (34%) and the oropharynx (30%). The response rate to TPF was 84%, including 26% with a complete response. Radiotherapy had been provided to 144 (92%) patients (of whom 17 had received radiotherapy alone, 46 had received q3w cisplatin, 30 had received q1w cisplatin, and 37 had received cetuximab). Potentiation had been achieved as planned in 59, 63, and 62% of patients treated with q3w cisplatin, q1w cisplatin, and cetuximab, respectively. After a median follow-up of 39.9 months, the median overall survival was 43 months. No significant difference was observed in progression-free survival or overall survival according to the type of potentiation. This study confirms the efficacy and tolerability of TPF induction, followed by chemoradiation, with outcomes similar to those for patients irradiated without induction. The best potentiation of radiotherapy after induction has not yet been determined.

Efficacy and safety of capecitabine in heavily pretreated recurrent/metastatic head and neck squamous cell carcinoma.

The objective of this study was to evaluate the efficacy and tolerability of capecitabine as a single agent in the treatment of recurrent/metastatic head and neck squamous cell carcinoma. Patients were treated with oral capecitabine according to good clinical practice. Efficacy and safety outcomes were analyzed retrospectively. The response and adverse events rates and their exact confidence intervals (CIs) were calculated. Survival distributions were estimated using the Kaplan–Meier method. Twenty-nine patients were included in the study. Twenty-five patients (86%) had received at least three previous lines of chemotherapy. The disease control rate was 48% (95% CI: 29–67%). The median progression-free survival was 2.0 months (95% CI: 0.1–3.9 months) and the median overall survival was 7.0 months (95% CI: 4.1–9.9 months). Hand–foot syndrome, fatigue, and mucositis were the most frequent severe side effects. No patient died, and only three patients discontinued treatment because of side effects. Capecitabine seems to be an active and well-tolerated regimen, even in heavily pretreated, frail patients. Level of evidence: 2C ‘Outcomes Research’.

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.

Neoadjuvant modified TPF (docetaxel, cisplatin, fluorouracil) for patients unfit to standard TPF in locally advanced head and neck squamous cell carcinoma: a study of 48 patients

TPF (docetaxel, cisplatin, fluorouracil) is the standard chemotherapy used for induction in locally advanced head and neck squamous cell carcinoma (LAHNSCC). Its toxicity limits it to younger patients with good functional status and without significant comorbidity. Since modified TPF (mTPF) demonstrated higher tolerability with similar efficacy in gastric cancer, we tested this scheme on frail patients. From July 2010 to July 2014, the files of the 48 patients treated for LAHNSCC with mTPF in three French institutions were retrospectively collected. mTPF was chosen because of age>70 years, or severe denutrition, or PS>1, or severe comorbidities or after severe toxicity of standard TPF. During the first 4 cycles, 2 patients died, 14 secondary hospitalizations were required and 10 patients stopped treatment due to no lethal toxicity. Two patients died during radiotherapy. The response rate was 83% (19% complete response). With a median follow-up of 15.2 months, 4 patients died during treatment, 8 died of non-head and neck cancer related disorders, 18 progressed (17 deaths) and 18 were free of disease. The median overall survival was 18.5 months (95% IC: 16.9-30.0). mTPF is effective in terms of response rate compared with the standard TPF and could become a new option in induction for frail patients with LAHNSCC.