Protontherapy of head and neck paragangliomas: A monocentric study

Purpose

The aim of this study was to assess efficacy and safety of proton beam therapy of paragangliomas of the head and neck, rare benign tumours developed close to crucial structures such as cranial nerves and vascular tissues.

Effect of lymphoid volume irradiation on radiation-induced lymphopenia in head and neck cancers

PurposeRadiotherapy induces significant and prolonged lymphopenia in head and neck cancer patients with poorer outcomes and reduced survival. Irradiated volumes may be correlated with lymphopenia with a potential impact on immunotherapy efficacy. We assessed associations between volumes treated with radiotherapy and the nadir of the lymphocyte count in patients with head and neck cancer.Materials and methodsWe conducted a monocentric retrospective study in patients with head and neck cancer treated with radiation. Univariate analysis used regression analysis to model nadir lymphocyte count and radiotherapy volumes; multivariate analysis then modelled factors associated with nadir lymphocyte count.ResultsOf the 77 included patients, 97% presented lymphopenia during radiotherapy with an average nadir of 431 cells/mm³ at a median of 40 days after the beginning of treatment. The volume of high-risk radiotherapy and gross tumour volume were correlated with nadir lymphocyte count with a Spearman coefficient of −0.267 (P = 0.019) and −0.387 (P = 0.001), respectively. After multivariate linear regression, high-risk radiotherapy was significantly associated with nadir lymphocyte count with a regression coefficient of −0.32 (per cubic centimetre) [95% CI = −0.60; −0.03] (P = 0.028).ConclusionHigh-risk radiotherapy was significantly associated with nadir lymphocyte count in patients with head and neck cancer treated with radiation. Sparing lymphoid volumes from irradiation by elective nodal irradiation or proton therapy may limit lymphopenia and needs to be investigated in combination with immunotherapy.     

Impact du curage ganglionnaire cervical dans la prise en charge par chimioradiothérapie exclusive des cancers de l’oropharynx de stade N2-3 : étude observationnelle en vie réelle

PurposeThe purpose of this study was to assess the efficacy in terms of neck failure of an initial neck dissection before definitive chemoradiotherapy in N2-3 oropharyngeal squamous cell carcinomas, as well as the dosimetric impact and the acute and delayed morbidity of this approach.Materials and methodsAll patients consecutively treated between 2009 and 2018 with definitive chemoradiotherapy using intensity-modulated conformal radiotherapy (IMRT) for a histologically proven N2-3 oropharyngeal squamous cell carcinomas were retrospectively included. The therapeutic approach consisted of induction chemotherapy, followed by cisplatine-based chemoradiotherapy preceded or not by neck dissection. Neck dissection was discussed on a case-by-case basis in a dedicated multidisciplinary tumour board for patients with a dissociated response to induction chemotherapy, defined as a better response on the primary than on the node. Chemoradiotherapy without neck dissection was systematically performed in case of a major lymph node response to induction chemotherapy (decrease in size of 90% or more). Intensity-modulated radiotherapy using a simultaneous-integrated boost delivered 70 Gy in 35 fractions on macroscopic tumour volumes, 63 Gy on intermediate-risk levels or extra-nodal extension and 54 Gy on prophylactic lymph node areas.ResultsTwo groups were constituted: 47 patients without an initial neck dissection (62.7%), and 28 patients with a neck dissection prior to definitive chemoradiotherapy (37.3%). Initial patient characteristics were not statistically different between the two groups. The median follow-up was 60.1 months (range: 3.2–119 months). Incidence of neck failure was higher in patients without neck dissection (P = 0.015). The neck failure rate at 5 years was 19.8% (95% confidence interval: 7.4–30.6%; P = 0.015) without neck dissection versus 0% following neck dissection. All lymph node failures occurred in the planned target volume at 70 Gy. Upfront neck dissection suggested a decrease in the mean dose received by the homolateral parotid gland (P = 0.01), mandible (P = 0.02), and thyroid gland (P = 0.02). Acute toxicity of chemoradiotherapy after neck dissection suggested a reduction in grade ≥ 3 adverse events (P = 0.04), early discontinuation of concomitant chemotherapy (P = 0.009) and feeding tube-dependence (P = 0.008) in univariate analysis. During follow-up, there was no difference between the two groups in terms of xerostomia, dysgeusia, dysphagia or gastrostomy dependence in univariate analysis.ConclusionNeck dissection prior to definitive chemoradiotherapy in N2-3 oropharyngeal squamous cell carcinoma was associated with high neck control without additional mid and long-term morbidity.     

Systematic dosimetric evaluation of risk of osteoradionecrosis (DERO): First results of dose reporting for preventing teeth osteoradionecrosis after head and neck irradiation

PurposeOsteoRadioNecrosis (ORN) is a late complication of radiation for head and neck cancer. Predicting ORN is a major challenge. We developed DERO (Dosimetric Evaluation of Risk of ORN), a semi-automatic tool which reports doses delivered to tooth-bearing sectors, to guide post-therapeutic dental care. We present the method and the first results of a 125-patient prospective cohort.Material and methodsDosimetric data of patients treated with IMRT for head and neck cancer were prospectively segmented to the DERO algorithm. Four arches corresponding to 8-tooth sectors were semi-automatically generated. Thirty-two cylindrical Regions Of Interest (ROI) corresponding to each tooth and surrounding periodontium were created by linear interpolation. Mean doses (Dmean) of ROI were extracted and included in a database, along with data about primary tumor site, laterality and dose values from organs at risk. Dmean to tooth sectors were computed for molar sectors, (teeth X5 to X8) and anterior sectors (teeth X1 to X4). An individual dose map was generated and delivered to patients and dentists.ResultsDosimetric data from 125 patients treated with Tomotherapy® were prospectively collected and analyzed: 9 parotid tumors (PA), 41 Sub-Hyoid tumors (larynx, hypopharynx) (SH), 43 Oropharynx tumors (OR), 32 Oral Cavity tumors (OC). Irradiation was unilateral for 100% of PA tumors (9), 12% of OR tumors (5) and 47% of OC tumors (15). For unilateral cervical irradiation, Dmean in ipsilateral molar sectors was 54 Gy for OC tumors, 45 Gy for OR tumors, 20 Gy for PA tumors. For Oral Cavity bilateral irradiation, Dmean was high in all tooth sectors, 49 to 55 Gy. For SH tumors, Dmean in molar sectors was 27 Gy. A dose gradient of 10 to 20 Gy was observed between molar and anterior sectors whether radiation was uni or bilateral.ConclusionMandibular molar sectors of Oropharynx and Oral Cavity tumors were exposed to high Dmean of 40 to 50 Gy. On the other hand, tooth sectors received lower doses for SH radiation. The DERO tool guide post-radiation dental care with a personalized dosimetric cartography to patient. With data update and patient follow-up, we will be able to determine ORN risk after head and neck radiation.     

What to expect from immediate salvage hysterectomy following concomitant chemoradiation and image-guided adaptive brachytherapy in locally advanced cervical cancer

PurposeConcomitant chemoradiation followed by brachytherapy is the standard treatment for locally advanced cervical cancers. The place of adjuvant hysterectomy remains unclear but tends to be limited to incomplete responses to radiotherapy or local relapse. The aim was to analyse the benefit from immediate salvage surgery following radiation therapy in incomplete responders.MethodsAmong the patients with locally advanced cervical cancer treated with concomitant chemoradiation followed by 3D image-guided adaptive brachytherapy and hysterectomy, cases with genuine macroscopic remnant, defined as at least 1 cm in width, were identified. Their clinical data and outcomes were retrospectively reviewed and compared to the patients treated with the same modalities.ResultsFifty-eight patients were included, with a median follow-up of 4.2 years. After hysterectomy, 9 patients had macroscopic residual disease, 10 microscopic and the remaining 39 patients were considered in complete histological response. The 4-year overall survival and disease-free survival rates were significantly decreased in patients with macroscopic residual disease: 50 and 51% versus 92% and 93%, respectively. Intestinal grades 3–4 toxicities were reported in 10.4% and urinary grades 3–4 in 8.6% in the whole population without distinctive histological features. Planning aims were reached in only one patient with macroscopic residuum (11.1%). In univariate analysis, overall treatment time (> 55 days) and histological subtype (adenocarcinomas or adenosquamous carcinomas) appeared to be significant predictive factors for macroscopic remnant after treatment completion (P = 0.021 and P = 0.017, respectively). In multivariate analysis, treatment time was the only independent factor (P = 0.046, odds ratio = 7.0).ConclusionsAlthough immediate salvage hysterectomy in incomplete responders provided a 4-year disease-free survival of 51%, its impact on late morbidity is significant. Efforts should focus on respect of treatment time and dose escalation. Adenocarcinoma might require higher high-risk clinical target volume planning aims.     

Toxicity and efficacy of cetuximab associated with several modalities of IMRT for locally advanced head and neck cancer

PurposeIntensity-modulated radiation therapy (IMRT) has shown its interest for head and neck cancer treatment. In parallel, cetuximab has demonstrated its superiority against exclusive radiotherapy. The objective of this study was to assess the acute toxicity, local control and overall survival of cetuximab associated with different IMRT modalities compared to platinum-based chemotherapy and IMRT in the ARTORL study (NCT02024035).Patients and methodThis prospective, multicenter study included patients with epidermoid or undifferentiated nasopharyngeal carcinoma, epidermoid carcinoma of oropharynx and oral cavity (T1–T4, M0, N0–N3). Acute toxicity, local control and overall survival were compared between groups (patients receiving cetuximab or not). Propensity score analysis at the ratio 1:1 was undertaken in an effort to adjust for potential bias between groups due to non-randomization.ResultsFrom the 180 patients included in the ARTORL study, 29 patients receiving cetuximab and 29 patients treated without cetuximab were matched for the analysis. Ten patients (34.5%) reported acute dermal toxicity of grade 3 in the cetuximab group versus three (10.3%) in the non-cetuximab group obtained after matching (P = 0.0275). Cetuximab was not significantly associated with more grade 3 mucositis (P = 0.2563). There were no significant differences in cutaneous or oral toxicity for patients treated with cetuximab between the different IMRT modalities (P = 1.000 and P = 0.5731, respectively). There was no significant difference in local relapse-free survival (P = 0.0920) or overall survival (P = 0.4575) between patients treated with or without cetuximab.ConclusionPatients treated with cetuximab had more cutaneous toxicities, but oral toxicity was similar between groups. The different IMRT modalities did not induce different toxicity profiles.     

Adaptive radiotherapy using helical tomotherapy for head and neck cancer in definitive and postoperative settings: initial results

AimsTo assess whether routine mid-treatment replanning in head and neck squamous cell carcinoma patients results in meaningful improvements in target or normal tissue dosimetry and to assess which patients derive the greatest benefit.Materials and methodsTwenty patients treated with either postoperative chemoradiotherapy or definitive chemoradiotherapy with primary or nodal disease ≥3 cm in size were included in this prospective pilot study. Seven patients received adjuvant chemoradiotherapy and 13 received definitive chemoradiotherapy. Patients were planned and treated on a helical tomotherapy system. All patients had a second computed tomography scan after 15 fractions and a new plan based on this was initiated from fraction 20.ResultsRelative volume changes between computed tomography scans were: GTV 29%; CTV60 (adjuvant patients) 4%; parotid volume 17.5%; median reduction in neck separation 6–7 mm; weight loss 3%. For the group overall and for the definitively treated patient cohort, respectively, adapted plans resulted in reductions in PTV66 D₁ (0.3 Gy, P = 0.01 and 0.5 Gy, P = 0.01); PTV54 D₁ (0.6 Gy, P < 0.0001 and 0.9 Gy, P = 0.0002); spinal cord maximum (0.5 Gy, P = 0.004 and 0.6 Gy, P = 0.04) and volume of skin receiving ≥50 Gy (16 cm², P = 0.01 and 19 cm², P = 0.001). Definitively treated patients also had a reduction in mean parotid dose (0.6 Gy, P = 0.046) and volume of normal tissue receiving ≥50 Gy (67 cm³, P = 0.02). Patients with nasopharyngeal carcinoma received the greatest benefits with treatment adaptation with reduction in spinal cord maximum 1.2 Gy, mean parotid dose 1.2 Gy and parotid V₂₆ 6.3%. There was no significant benefit for adjuvant patients. Other factors associated with greater benefits were greater weight loss and greater reduction in neck separation and higher T stage.ConclusionsThere is minimal benefit to routine adaptive replanning in unselected patients, and no benefit in adjuvantly treated patients. Patients with nasopharyngeal carcinoma or with greater weight loss or reduction in neck separation did have clinically significant benefits. These patients should be targeted for adaptive strategies.     

Impact of geriatric assessment on the management of older adults with head and neck cancer: A pilot study

ObjectiveAssess the utility of the G8 screening tool and CGA for older adults with head and neck cancer.MethodsPatients 65 years or older with a primary malignancy of the head and neck region were presented at the multidisciplinary team (MDT) meeting. The Geriatric 8 (G8) questionnaire was administered prior. Clinicians, blinded to the G8 result, made a recommendation on appropriate treatment, including potential referral for CGA. Patients considered vulnerable (G8 score ≤ 14) were also to be referred for CGA. Treatment outcomes were recorded.ResultsOver 6 months, 35 patients were recruited, median age 74 (range 65–93). Seventeen (49%) patients were assessed as vulnerable by the G8 score, including 7 (20%) whom the MDT referred for CGA. Seven with G8 scores ≤ 14 did not receive a CGA. Thirty (85.7%) underwent curative intent treatment, including 6 of 7 who had CGA. Of 10 vulnerable patients who did not have CGA, 70% received curative-intent treatment. Mean length of post-operative stay was 12.2 vs. 6.5 days in patients deemed vulnerable or fit by G8 scores, respectively (p = 0.46); completion rate of radical radiotherapy was 75% vs. 100% in each group, respectively (p = 0.13). Mean post-operative length of stay in vulnerable patients who underwent a CGA was 6.2 days vs. 17.3 days in those who were not referred (p = 0.79).ConclusionsThe G8 tool identified twice the number of patients as vulnerable compared to the MDT. There was a trend towards longer postoperative stay and lower radiotherapy completion rates in patients deemed vulnerable by G8 scores.     

Patterns of care in older patients with squamous cell carcinoma of the head and neck: A Surveillance,Epidemiology, and End Results-Medicare analysis

BackgroundThere is growing evidence in the literature that older patients may not benefit from more intensive therapy for head and neck squamous cell carcinoma (HNSCC). A growing number of patients with HNSCC are age 65 years or older; however, much of the evidence base informing treatment decisions is based on substantially younger and healthier clinical trial populations. The purpose of this study was to assess the patterns of care of older HNSCC patients to better understand how age is associated with treatment decisions.MethodsUsing the Surveillance, Epidemiology, and End Results (SEER)-Medicare database (1992–2007), we identified patients with non-metastatic HNSCC (n = 10,867) and categorized them by treatment: surgery vs. non-surgery and chemoradiotherapy (CRT) vs. radiotherapy (RT). Multivariate logistic regression models were used to identify variables associated with the receipt of surgery and CRT.ResultsIncreasing age was associated with decreased odds of receiving CRT (OR = 0.94; 95% CI 0.93–0.94) but not surgery (OR 1.00; 95% CI 0.99–1.00). Co-morbidity and race were not associated with receipt of either surgery or CRT. Utilization of CRT increased while surgery decreased between 1992 and 2007.ConclusionAge may influence the receipt of CRT for older HNSCC patients. There has been an increasing trend in the receipt of CRT and a decrease in primary surgery.     

Medulloblastoma in childhood: What effects on neurocognitive functions?

PuposeMedulloblastoma is the most common primary malignant central nervous system tumor in childhood, accounting for 16–25% of cases (1). New treatment approaches have led to improved survival rates; however toxicities are still a major concern.Patients and methodsParticipants were selected from the records of patients who were treated with craniospinal irradiation for medulloblastoma. Between January 2008 and December 2012, 62 patients were diagnosed with medulloblastoma at the national institute of oncology Rabat, 27 patients were still alive at the time of the study, of which n = 16 patients were included in the study. The mean age of patients at the time of the study was 9.6 years. All children were treated with radiation therapy and chemotherapy, according to standard protocols. Median follow-up between treatment and evaluation was 4 years. All the children were assessed with the Wechsler Intelligence Scale for Children - fourth Edition (WISC-IV) three to five years after completion of radiotherapy. The test was administered by two well-trained psychologists in a distraction-free environment. The scoring was then reviewed by a psychologist from Brooklyn College.ResultsThe mean standard score Full-Scale Intelligence Quotient (FSIQ) (M = 63, SD = 12.6) was found to be in the extremely low range and in the 1st percentile rank (PR), compared to the general population. All the measured primary index scales were below typical performance: verbal comprehension (M = 67.7, SD = 13.1), perceptual reasoning (M = 63.5, SD = 13.8) and processing speed (M = 62.7, SD = 15.5) were all found to be in the extremely low range, while xorking memory (M = 75.5, SD = 10.8) was found to be in the borderline range compared to the general population. To identify factors influencing the results, we performed both univariate and multivariate analyses. Age at the time of radiotherapy, initial clinical stage, total cranial radiotherapy dose, socioeconomic status, and the time of evaluation were identified as significantly impacting cognitive scores in the univariate analysis. In the multivariate analysis, only age at the time of radiotherapy and initial clinical stage remained factors significantly impacting cognitive outcomes with P = 0.001 and P < 0.001 respectively.ConclusionOur study is evidence that tremendous efforts are still to be made in low-income countries to correctly measure neurocognitive dysfunction in medulloblastoma survivors and to prepare those patients to a typical life after the completion of treatment.     

Époétine bêta dans le traitement de l'anémie liée à la chimiothérapie dans les tumeurs solides et les hémopathies malignes. Résultats d'un essai clinique,en ouvert,multicentrique

AimEvaluate efficacy and safety of epoetin beta in anaemic patients receiving chemotherapy for a non-myeloid malignancy.Patients and methodsThis open-label, multicentric, clinical trial was conducted in France among 691 anaemic patients (haemoglobin ≤ 12 g/dL) with a solid or haematological malignancy to evaluate the benefit of epoetin beta 30,000 IU/week subcutaneously for 16 weeks. The primary endpoint was the rate of therapeutic response.ResultsThe overall response rate was 60.4% (CI 95%: [56.6%-64.1]). According to initial haemoglobin level < 11 g/dL or between 11 and 12 g/dL, it was 61.2% and 57.5% respectively. Response rates by tumour type (solid and haematological) were similar. The mean haemoglobin level increases were respectively 1.1 g/dL, approximately 2 and 2.2 g/dL at 4, 9, and 12 weeks after treatment initiation. In patients with haemoglobin level < 11 g/dL at inclusion the mean increases in haemoglobin level were respectively 1.17, 2.03 and 2.45 g/dL at 4, 9 and 12 weeks. During study period, 23% of patients required red blood cell transfusion. Overall treatment with epoetin beta was well-tolerated and 7.1% of patients only experienced thromboembolic events.ConclusionFor treating chemotherapy-induced anaemia in patients with solid or haematological malignancy (especially if haemoglobin level < 11 g/dL), epoetin beta 30.000 IU subcutaneously once-weekly (450 IU/kg/week) is rapidly effective and overall well-tolerated.     

Use of an intravaginal spacer in young girls treated with brachytherapy for bladder neck rhabdomyosarcoma: Dosimetric impact for organs at risk sparing and acute tolerance

PurposeInterstitial brachytherapy is indicated as part of a conservative strategy for children with bladder and/or prostate rhabdomyosarcoma (RMS), providing high local control probability with acceptable functional results. Vaginal and/or rectal complications were however reported, due to the close proximity to the implanted volume. We investigated the dosimetric impact of a vaginal spacer in terms of rectal and vaginal doses.Methods and patientsMedical records of 12 consecutive female patients with bladder neck RMS, median age 32 months (range: 1.3–6 years), were reviewed. Five patients were treated prior to 2017 without a vaginal spacer and seven patients treated after 2017 had their brachytherapy delivered with a vaginal spacer placed at time of implant.ResultsMinimal doses delivered to the most exposed 2 cm³, 1 cm³, and 0.5 cm³ of the rectum were all statistically significantly lower among patients treated with a vaginal spacer, as compared to those treated without a spacer. Median rectal D2cm³ was 22 Gy_EQD2 versus 38 Gy_EQD2 (P = 0.02), D1cm³ was 29 Gy_EQD2 versus 51 Gy_EQD2 (P = 0.013), and D0.5cm³ was 32 Gy_EQD2 versus 61 Gy_EQD2 (P = 0.017), with and without the vaginal spacer, respectively. The posterior vaginal wall D0.5cm³ dose was also significantly decreased, with median D0.5cm³ of 92 Gy_EQD2 versus 54 Gy_EQD2 (P < 0.0001), with and without the spacer, respectively. Acute tolerance was excellent in all patients, with no need for replanning and no acute complication.ConclusionsThe use of vaginal spacers in brachytherapy of female pediatric patients with bladder neck RMS resulted in significantly decreased doses to the rectum and the posterior vaginal wall. Though the clinical impact of such dose reduction remains undemonstrated, routine utilization of a vaginal spacer could be a method to decrease long-term morbidity in these patients.     

Prediction of prognosis after trimodal therapy in patients with locally advanced squamous cell carcinoma of the oesophagus

BackgroundDue to the poor prognosis of locally advanced oesophageal cancer, predictive markers are warranted to better select patients who may benefit from multimodal therapy.Patients and methodsPatients with oesophageal cancer from two multicentric prospective trials were selected for having received radiochemotherapy followed by macroscopic complete tumour resection. Several pretreatment and treatment related factors were retrospectively analysed for their ability to serve as predictive markers.ResultsOverall 107 patients with squamous cell carcinomas stage T3-4 N and M0 were included in the analysis. All of them had complete preoperative radiochemotherapy. Microscopic (n = 96) or macroscopic (N = 11) complete resection was achieved by transthoracic oesophagectomy. The median follow-up time exceeded 6 years. Local progression free and overall survival were significantly hampered in patients with residual tumour in their resected specimen (n = 76) compared with patients who showed a pathohistologic complete tumour remission (n = 31) (overall survival rate at 3 years 25.2% versus 65.6%; hazard ratio (HR) = 3.50 (95%-confidence interval (CI) 1.91–6.44); p < 0.0001). A multivariable analysis proved both resection status and pathohistologic results to be independent acting predictive factors for local progression free and overall survival after preoperative radiochemotherapy with surgery.ConclusionsFrom our study it appears that the pathohistologic results can be a valuable surrogate marker for predicting long term survival and local tumour control in patients with locally advanced squamous cell carcinoma (SCC) of the oesophagus after preoperative radiochemotherapy and surgery. Moreover, even after intensive preoperative therapy a complete tumour resection seems to be an important precondition for long term survival.     

Présentation de l’étude Gortec 2017-03 : radiothérapie en conditions stéréotaxiques postopératoire des cancers localisés de l’oropharynx et de la cavité buccale avec marges à risque (PHRC-K-16-164)

The GORTEC 2017-03-Stereo-postop study is a phase 2, multicentric, nationwide study, funded by the hospital clinical research program (PHRC). The sponsor is Centre Jean-Perrin in Clermont-Ferrand, in partnership with the GORTEC. The principal investigators are Dr J Biau and Dr M Lapeyre. The main objective is to study severe late toxicity of postoperative stereotactic radiotherapy (6 × 6 Gy) for early stage oropharyngeal and oral cavity cancer with high risk margins. The secondary objectives include acute toxicity, efficacy, nutritional impact and quality of life. The population is adult patients, with pT1 or pT2 squamous cell carcinoma of the oropharynx or oral cavity (except lips), without indication of neck irradiation or concomitant chemotherapy, with at risk margin (R1, less than 5 mm or uncertain). Ninety patients will be included over a 2-year period; this was calculated to limit the rate of 2-year severe toxicity at 5 to 15%, with a 2-year local control of at least 80 to 90%. If this study is considered as positive, stereotactic radiotherapy (6 × 6 Gy) could become the third therapeutic option, with brachytherapy and normofractionated intensity-modulated radiotherapy (IMRT), for postoperative irradiation of oropharyngeal and oral cavity cancer with high risk margins.     

Radiotherapy combined with cetuximab for locally advanced head and neck cancer: Results and toxicity

PurposeTo describe the clinical results and tolerance of the combined treatment with radiotherapy and cetuximab for locally advanced head and neck cancer.Patients and methodsFrom August 2006 and October 2010, 36 patients with advanced squamous cell head and neck carcinoma were treated with radiotherapy (70 Gy/35 fractions) and cetuximab (400 mg/m² one week before radiotherapy, following by 250 mg/m² once weekly, until week 7 of radiotherapy). Tolerance was evaluated every week. All patients were examined every 3 months the first 3 years after therapy, and then every year.ResultsThe median follow-up was 14 months. The majority of patients were male (31 out of 36). Mean age was 59 years. The tumours sites were: oral cavity (n = 8); oropharynx (n = 15); hypopharynx (n = 5); larynx (n = 8). Ninety percent of tumors were T3 or T4, and 45% were N2 or N3. Complete response was seen in 74% of patients, partial response in 17% and no response in 9% of patients. The overall survival was 44.4%. Relapse occurred in six patients. Anaphylactic reaction during the first infusion of cetuximab was observed in one patient. One patient developed severe aplasia after 48 Gy and 5 weeks of cetuximab, and died of sepsis. Eighty percent of patients presented acne, 16 patients developed a mucositis grade 2–3 and 23 patients a grade 2 skin reaction.ConclusionThe concomitant use of cetuximab and radiotherapy in locally advanced head and neck carcinoma is well tolerated in this group of patients. The results seem comparable to those in the literature.     

Induction chemotherapy with docetaxel,cisplatin and 5-fluorouracil followed by radiotherapy with cetuximab for locally advanced squamous cell carcinoma of the head and neck

PurposeTo determine the efficacy and feasibility of induction chemotherapy (ICT) with docetaxel, cisplatin and 5-fluorouracil followed by radiotherapy and cetuximab (C) in patients with locally advanced head and neck cancer.Patients and methodsForty-nine previously untreated patients with local advanced stage III and IV squamous cell carcinoma of the head and neck (SCCHN) received three courses of ICT consisting of docetaxel 75 mg/m² day 1, cisplatin 75 mg/m² day 1 and infusional 5-fluorouracil 750 mg/m²/day on days 1–5 followed by radiotherapy plus C at 250 mg/m²/week (after an initial loading dose of 400 mg/m²).ResultsAfter completion of ICT 44 of 49 patients received radiotherapy plus C. Three months after therapy completion tumour response was observed in 33 patients and after two years, 25 patients were in complete remission (CR). The most common grade 4 toxicity during the whole treatment period was dermatitis (30%), followed by mucositis (27%) and neutropenia (17%) without fever. One toxic related death was observed during ICT. Two-year progression-free survival (PFS) rate was 59% and two-year overall survival (OS) rate was 63%, respectively.ConclusionConcurrent radiotherapy plus C after three courses of ICT was feasible and was associated with promising CR, PFS and OS rates. Further optimisation of dose and sequence is warranted.     

Pattern of relapse following three-field lymphadenectomy of esophageal carcinoma and related factors predictive of recurrence

PurposeFor treatment of esophageal carcinoma, the optimal postoperative radiotherapy target volume after three-field lymph node dissection (3-FLD) had not been determined. We analyzed local recurrence pattern of thoracic esophageal carcinoma and risk factors of lymph node recurrence after 3-FLD without prophylactic radiotherapy.Material and methodsWe reviewed 1282 patients with thoracic esophageal squamous cell carcinoma (ESCC) who were treated with 3-FLD without radiotherapy from 2010 to 2018 and analysed local recurrence patterns and risk factors of lymph node recurrence, in order to provide a reference for determination of the radiotherapy target volume for thoracic ESCC.ResultsThe lymph node recurrence accounted for 91.0% of treatment failures. The mediastinal, cervical and abdominal lymph node recurrence accounted for 84.92%, 36.07% and 22.30%, respectively (χ² = 264.776, P = 0.000). The superior, middle and inferior mediastinal lymph node recurrence rates were 67.54%, 27.87% and 0.98%, respectively (χ² = 313.600, P = 0.000). Cervical metastases were significantly associated with N stage and Preoperative cervical lymph node status. Abdominal metastases were significantly associated with the number of preoperative abdominal lymph node metastases (LNM), tumor location and N stage.ConclusionsThe main pattern of local-regional recurrence might be lymph node metastasis after radical 3-FLD without radiotherapy in esophageal carcinoma. The dangerous lymph node recurrence regions included neck, superior and middle mediastinum. The abdominal areas might be irradiated for lower TEC patients with preoperative abdominal LNM.     

Single French centre retrospective analysis of local control after high dose radiotherapy with or without chemotherapy and local control for Pancoast tumours

PurposeSuperior sulcus non-small cell lung cancer represents less than 5% of all lung cancers and is a challenge for the physicians because of clinical presentation, treatments related toxicities and poor prognosis. The aim of this preliminary retrospective report is to present outcomes of patients affected by a superior sulcus non-small cell lung cancer, treated by high dose radiotherapy (> 60 Gy) with or withour chemotherapy.Patients and methodsAll adult inoperable or unresectable patients (≥ 18 years) with a clinical and radiological diagnosis of superior sulcus non-small cell lung cancer treated in our department by radiotherapy with or without chemotherapy were retrospectively analysed. Primary endpoint was the local control. Overall survival, metastasis free survival and toxicity rates were also analysed and reported.ResultsFrom January 1999 to June 2009, 12 patients were treated by exclusive high-dose radiochemotherapy. Median age was 53 years (range: 33–64 years); mean follow-up time was 20 months (range: 2–75 months). Mean local control, overall survival and metastasis free survival were 20.2, 22 and 20 months, respectively. At the time of this analysis, seven patients died of cancer and three of them presented only a metastatic disease progression. One patient died of acute cardiac failure 36 months after the end of radiochemotherapy and was disease free. Treatment was well tolerated and any acute and/or late G3-4 toxicity was recorded (NCI-CTC v 3.0 score).ConclusionThis analysis confirms the interest of exclusive high-dose radiochemotherapy in treating inoperable superior sulcus non-small cell lung cancer patients, in achieving good local control and overall survival rates.