Philippe Zrounba

Conformal radiotherapy for paranasal sinus and nasal cavity tumors: three-dimensional treatment planning and preliminary results in 40 patients

PURPOSE To assess the possibility to deliver a high and homogeneous irradiation with respect to maximal tolerated dose to the visual pathways for paranasal sinus and nasal cavity tumors. METHODS AND MATERIALS Forty patients with advanced stage malignant tumors were treated with postoperative (30) or primary (10 patients) conformal radiotherapy (CRT). Five patients were previously irradiated. Six to 15 individually shaped isocentric noncoplanar field arrangements, using a multileaf collimator were designed. Dose-volume histograms (DVH) for the planning target volumes (PTV) and the optic pathways were analyzed in 31 cases. RESULTS Median and maximal delivered doses to the PTV were 60 (+/-3) and 66 (+/-4) Gy. Dose distributions for critical organs are detailed. Median follow-up was 19 months (3 to 48). Local, nodal, and metastatic recurrences occurred in 8, 2, and 7 cases, respectively. Major prognostic factor for local recurrences was central nervous system (CNS) involvement. One patient died of meningitis. Two patients developed cataract, and 1 patient ipsilateral blindness due to vascular glaucoma. CONCLUSION CRT for locally advanced paranasal sinus and nasal cavity tumors enables the delivery of high homogeneous doses to the PTV with respect to critical organs, with a low toxicity and a high local control.

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.

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.

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.

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/m2) or weekly (80 mg/m2). 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.

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’.

A new, simple maxillary‐sparing tongue depressor for external mandibular radiotherapy: A case report

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.

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.

A pyriform sinus cancer organ preservation strategy comprising induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil, followed by potentiated radiotherapy: a multicenter, retrospective study.

No specific study has evaluated the role of neoadjuvant DCF (docetaxel, cisplatin, 5-fluorouracil) followed by radiotherapy in pyriform sinus cancer, which are often included in studies focusing on laryngeal and hypopharyngeal cancer. We assessed the proportion of patients treated sequentially for a pyriform sinus cancer with a preserved larynx. Overall survival, event-free survival (EFS), survival with ‘local control’, and treatment tolerance were assessed as well. We retrospectively reviewed 88 patients with advanced pyriform sinus squamous cell carcinoma treated with DCF between 2005 and 2010. After induction, radiation could be potentiated with cetuximab or cisplatin. Most patients (82%) had been treated with organ preservation intent. The response rate to DCF was 85%, including 42% with complete response. Primary tumor was operated in 13 patients (eight with total laryngectomy). Radiotherapy had been delivered to 78 (89%) patients (30 with cisplatin, 39 with cetuximab). Potentiation had been achieved as planned in 52 and 79% of patients treated with cisplatin and cetuximab, respectively. Twenty-three local and three neck recurrences were found. Median overall survival was 16.8 months and 38.3% at 3 years. EFS at 3 years was 29.1% with a hazard ratio for partial responders versus nonresponders of 0.18 (P<0.001), and 0.13 (P<0.001) for complete responders versus nonresponders. Thirty-five percent of patients were alive with their larynx preserved at 3 years. This study confirms the efficacy of induction followed by chemoradiation for pyriform sinus cancer and that response to DCF is predictive of EFS.