Definitive Chemoradiotherapy with Docetaxel, Cisplatin, and 5-Fluorouracil for Advanced Cervical Esophageal Cancer: A Medium-Term Outcome.

BACKGROUND: Definitive chemoradiotherapy (dCRT) is widely considered as a treatment option for cervical esophageal squamous cell carcinoma (ESCC) toward preserving the larynx. We have reported favorable outcomes, including the treatment response rate and short-term survival of dCRT concomitant with docetaxel, cisplatin, and 5-fluorouracil (DCF-RT) for advanced cervical ESCC. The aim of this paper was to report the subsequent progress of the study. METHODS: We assessed 18 patients with advanced (clinical stage II-IV, including T4b and/or M1 lymph node) cervical ESCC at our department who received DCF-RT as the first-line treatment between December 2010 and June 2020. RESULTS: A total of 14 men and 4 women underwent the study regimen. The pretreatment clinical stage included stage II, stage III, stage IVA, and stage IVB cases (including 9 patients with T4b) [8 trachea and 2 thyroids] and 7 patients with the M1 lymph node. The complete response (CR) was achieved in 15 patients, stable disease in 2, and progressive disease in 1. Of 15 patients with CR, 7 experienced recurrence, and 8 had continued CR. Frequent cases of grade ≥3 adverse effects included leucopenia, neutropenia, febrile neutropenia, and pharyngeal pain. The 3-year overall survival rate, disease-free survival rate, and disease-specific survival rate were 44.2%, 47.7%, and 48.6%, respectively. CONCLUSION: DCF-RT for advanced cervical esophageal cancer could achieve a favorable prognosis with larynx preservation. Further observations are warranted to establish the long-term prognosis, late complications of radiotherapy, and the significance of salvage surgery.

Oncological and Functional Outcomes of Larynx-preserving Surgery for Hypopharyngeal Cancer: A Comparison with Definitive Radiation-based Treatment.

PURPOSE: Larynx-preserving surgery (LPS) have recently gained popularity and achieved comparable oncologic outcomes to conventional radical surgery for localized hypopharyngeal cancer (HPC). In the current study, the role of LPS has been assessed thoroughly in comparison with upfront radiation therapy (RT). MATERIALS AND METHODS: We retrospectively reviewed 185 candidates for LPS with cT1-2 disease; 59 patients underwent upfront LPS while 126 patients received upfront RT, respectively. Oncological and functional outcomes were investigated and compared. RESULTS: Following LPS, safe margin (≥ 5 mm) was achieved in 37.3% of patients. Overall, better clinical outcomes at 5 years were achieved following upfront LPS than those following upfront RT: overall survival (OS) (72.7% vs. 59.0%, p=0.045), disease-free survival (DFS) (59.8% vs. 45.0%, p=0.039), and functional laryngeal preservation (100% vs. 89.7%, p=0.010). Although similar outcomes were observed in patients with cT1 disease, better 5-year DFS was achieved following upfront LPS in patients with cT2 disease (57.0% vs. 36.4%, p=0.023) by virtue of better local control. Despite frequent cN2-3 disease in upfront LPS group, comparable outcomes were observed between upfront RT and LPS group. However, multivariable analyses revealed that performance status and double primary cancer diagnosed within 6 months of HPC diagnosis affected OS significantly, while treatment modality per se did not. CONCLUSION: Although upfront LPS could provide better local control than upfront RT in patients with cT2 disease, overall outcomes were comparable following either modality. Treatment selection of larynx-preserving approach for HPC should be individualized based on tumor and patient factors.

[Radiotherapy for patients with early-stage glottic squamous cell carcinoma of the larynx: Interest of hypofractionation?] / Radiothérapie du carcinome épidermoïde du larynx de stade précoce, étage glottique : intérêt de l'hypofractionnement ?

Hypofractionated radiotherapy of early-stage squamous cell carcinoma of the glottic larynx is a promising treatment option. This can be divided into radiotherapy with moderate hypofractionation (up to 2.5Gy per fraction), more intense hypofractionation (between 2.5 and 4.5Gy per fraction) and stereotactic radiotherapy (above 4.5Gy per fraction). Most studies evaluating moderate hypofractionation show a local control rate between 85 and 95%. Acute laryngeal toxicity is superior to conventional treatment, but only for grades 1 and 2, with no significant difference reported for severe toxicity. Stereotactic radiotherapy in this pathology is also an emerging entity, but some authors have reported significant toxicity. There are currently no standardized guidelines for treatment and management regimen. We conducted a systemic review of published prospective and retrospective trials to evaluate efficacy, toxicity, and discuss future directions.

Vocal-cord Only vs. Complete Laryngeal radiation (VOCAL): a randomized multicentric Bayesian phase II trial.

BACKGROUND: Radiotherapy, along with laser surgery, is considered a standard treatment option for patients with early glottic squamous cell cancer (SCC). Historically, patients have received complete larynx radiotherapy (CL-RT) due to fear of swallowing and respiratory laryngeal motion and this remains the standard approach in many academic institutions. Local control (LC) rates with CL-RT have been excellent, however this treatment can carry significant toxicities include adverse voice and swallowing outcomes, along with increased long-term risk of cerebrovascular morbidity. A recent retrospective study reported improved voice quality and similar local control outcomes with focused vocal cord radiotherapy (VC-RT) compared to CL-RT. There is currently no prospective evidence on the safety of VC-RT. The primary objective of this Bayesian Phase II trial is to compare the LC of VC-RT to that of CL-RT in patients with T1N0 glottic SCC. METHODS: One hundred and fifty-five patients with T1a-b N0 SCC of the true vocal cords that are n ot candidate or declined laser surgery, will be randomized in a 1:3 ratio the control arm (CL-RT) and the experimental arm (VC-RT). Randomisation will be stratified by tumor stage (T1a/T1b) and by site (each site will be allowed to select one preferred radiation dose regimen, to be used in both arms). CL-RT volumes will correspond to the conventional RT volumes, with the planning target volume extending from the top of thyroid cartilage lamina superiorly to the bottom of the cricoid inferiorly. VC-RT volumes will include the involved vocal cord(s) and a margin accounting for respiration and set-up uncertainty. The primary endpoint will be LC at 2-years, while secondary endpoints will include patient-reported outcomes (voice impairment, dysphagia and symptom burden), acute and late toxicity radiation-induced toxicity, overall survival, progression free survival, as well as an optional component of acoustic and objective measures of voice analysis using the Consensus Auditory-Perceptual Evaluation of Voice. DISCUSSION: This study would constitute the first prospective evidence on the efficacy and safety of VC-RT in early glottic cancer. If positive, this study would result in the adoption of VC-RT as standard approach in early glottic cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03759431 Registration date: November 30, 2018.

Reconstructive Options During Nonfunctional Laryngectomy.

OBJECTIVE: A paucity of data exists regarding surgical outcomes for patients undergoing total laryngectomy for a dysfunctional larynx. Herein, we present the largest study evaluating the method of closure on postoperative fistula rate and swallowing ability. METHOD: We performed a retrospective review of patients undergoing total laryngectomy for a dysfunctional larynx after primary radiation or chemoradiation therapy for laryngeal carcinoma from 1998 to 2020. Demographic information, operative details, length of hospitalization, fistula formation, method of fistula treatment, and need for enteral feeding 6 months after surgery were analyzed. RESULTS: A total of 268 patients were included. Flaps were performed in 140 (52.2%) patients, including radial forearm free flaps (RFFF), pectoralis flaps, and supraclavicular flaps. Sixty-four (23.9%) patients developed postoperative fistulas. There was no significant difference in the fistula rate between flap and primary closure methods (P = .06). However, among patients who had a flap, RFFF had a significantly lower fistula rate (P = .02). Significantly more patients who had initial closure with a pectoralis flap required an additional flap for fistula repair than those who underwent RFFF or primary closure (P < .05). Last, whereas 87 patients (32.5%) required an enteral feeding tube 6 months after surgery, significantly fewer patients who underwent RFFF were feeding tube-dependent (P = < .0001). CONCLUSION: Herein, we present the largest study of outcomes after total laryngectomy for dysfunctional larynx. Postoperative fistula rates are high, 23%; however, the majority of patients, 67%, will not require long-term enteral support. The RFFF is an excellent option demonstrating the lowest rates of postoperative fistula and enteral feeding tube dependence. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1510-E1513, 2021.

Laser Microsurgery Versus Radiotherapy Versus Open Partial Laryngectomy for T2 Laryngeal Carcinoma: A Systematic Review of Oncological Outcomes.

INTRODUCTION: The aim of the current systematic review is to update the pooled survival outcome of patients with T2 glottic carcinoma treated with either laser surgery (CO2 transoral laser microsurgery [CO2 TOLMS]), radiotherapy (RT), or open partial laryngectomy (OPL). METHODS: A systematic search was performed using the MEDLINE database, Scopus, and Google scholar. The inclusion criteria were studies of patients with T2N0 glottic tumor, treated with either primary CO2 TOLMS, definitive curative RT, or primary OPL, and with reported oncological outcome at 5 years calculated with a Kaplan-Meier or Cox regression method. RESULTS: The results of the current review show that local control (LC) is higher with OPL 94.4%, while there are no differences in LC at 5-year posttreatment for patients treated with RT, compared to those treated with CO2 TOLMS (respectively, 75.6% and 75.4%). Primary treatment with OPL and CO2 TOLMS results in higher laryngeal preservation than primary treatment with RT (respectively 95.8%, 86.9%, and 82.4%). CONCLUSION: First-line treatment with OPL and CO2 TOLMS should be encouraged in selected T2 patients, because it results in higher laryngeal preservation and similar LC compared to primary treatment with RT. The involvement of the anterior commissure in the craniocaudal plane and T2b impaired vocal cord mobility have a poorer prognosis and LC compared to patients with T2a tumors for both CO2 TOLMS and RT.

Long-term Follow-up After Radiation Therapy for Laryngeal Amyloidosis.

OBJECTIVES: Laryngeal amyloidosis (LA) is a rare disease characterized by extracellular protein deposition within the larynx. Treatment is difficult due to the frequently submucosal and multifocal nature of disease. The mainstay of treatment is surgical resection; however, recurrence rates are high. Recently, use of radiotherapy (RT), either alone or postoperatively, for LA has been adapted from the management of extramedullary plasmacytoma and has been shown to provide local disease control. Here, we describe the experience with adjuvant RT for LA at our center. STUDY DESIGN: Retrospective case series. METHODS: Retrospective study of patients with amyloidosis of the larynx, with or without other disease sites, seen at a tertiary academic center between 2011 and 2019. Outcomes included disease characteristics, recurrence rates, treatment modalities, and pre- and posttreatment voice handicap index (VHI)-10. RESULTS: Ten patients met eligibility criteria. Mean follow-up time for all patients was 62.0 ± 41.0 months; mean follow-up time after last treatment was 51 ± 55 months. All but one patient underwent surgical resection of disease. Seven patients underwent subsequent RT. Of these seven, six underwent RT at our institution; five received a dose of 45 Gray (Gy); and one received a dose of 20 Gy. All seven completed RT without toxicity-related interruption. Patients undergoing RT underwent 2.1 ± 1.3 surgical procedures prior to RT; no patients required surgery after RT. Mean pretreatment VHI-10 was 22.9 ± 8.1; mean posttreatment VHI-10 was 12.9 ± 13.3. CONCLUSION: RT after surgery for LA can provide good local control without unacceptable toxicity and may decrease the need for further surgery. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1810-1815, 2021.

Perceptual Voice and Speech Analysis after Supraglottic Laryngeal Closure for Chronic Aspiration in Head and Neck Cancer.

OBJECTIVES/HYPOTHESIS: To evaluate the voice and speech outcomes after tubed supraglottic laryngeal closure (TSLC) surgery to treat chronic aspiration after radiotherapy for head and neck cancer. STUDY DESIGN: A retrospective case-control study. METHODS: The data of patients who underwent radiotherapy for head and neck cancer and who later required total laryngectomy or TSLC for chronic aspiration between 2004 and 2017 were retrieved from a dysphagia clinic. Preoperative and postoperative voice and speech were assessed by the GRBAS and INFVo rating scales. Control subjects who underwent radiotherapy alone or total laryngectomy with a tracheoesophageal prosthesis for other indications were recruited for comparison. RESULTS: Of 15 patients who underwent a TSLC with a mean age of 57.3 years (45-75 years), 13 were male and 2 female. All patients had a history of nasopharyngeal carcinoma. The success rate of speech production using their own larynx following an intact TSLC was 64%. There was no statistically significant difference in voice and speech ratings between preoperative and TSLC subjects on the GRBAS (P = .32) and INFVo scales (P = .57), although the quality of voice appeared to deteriorate after TSLC. However, the INFVo scale for impression, intelligibility and unsteadiness of the voice after TSLC was statistically significantly better than for laryngectomy with tracheoesophageal speech. CONCLUSIONS: A tubed supraglottic laryngeal closure controls chronic aspiration while preserving the larynx for phonation, and results in a better voice and speech quality than a laryngectomy with a voice prosthesis. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1616-E1623, 2021.

Routine restaging after primary non-surgical treatment of laryngeal squamous cell carcinoma-a review.

PURPOSE: Treatment of patients with laryngeal squamous cell carcinoma with radiotherapy or chemoradiation is an established alternative to laryngeal surgery in many cases, but particularly for advanced tumors without cartilage invasion. Imaging modalities face the challenge of distinguishing between posttherapeutic changes and residual disease in the complex anatomic subsite of the larynx. Guidelines concerning restaging of head and neck squamous cell carcinomas (HNSCC) are presented by the National Comprehensive Cancer Network (NCCN) and other national guidelines, but clearly defined recommendations for routine restaging particularly for laryngeal cancer are lacking. METHODS: A systematic search was carried out in PubMed to identify studies evaluating routine restaging methods after primary non-surgical treatment of laryngeal squamous cell carcinoma from 2009 to 2020. RESULTS: Only three studies were deemed eligible, as they included at least ≥50% patients with laryngeal squamous cell carcinoma and evaluated imaging modalities to detect residual cancer. The small number of studies in our review suggest restaging with fluoro-deoxy-glucose positron-emission tomography/computed tomography (FDG PET/CT) 3 months after initial treatment, followed by direct laryngoscopy with biopsy of the lesions identified by FDG PET/CT. CONCLUSION: Studies evaluating restaging methods after organ-preserving non-surgical treatment of laryngeal carcinoma are limited. As radiotherapy (RT), chemoradiotherapy (CRT), systemic therapy followed by RT and radioimmunotherapy are established alternatives to surgical treatment, particularly in advanced laryngeal cancers, further studies are needed to assess and compare different imaging modalities (e.g. PET/CT, MRI, CT, ultrasound) and clinical diagnostic tools (e.g., video laryngoscopy, direct laryngoscopy) to offer patients safe and efficient restaging strategies. PET or PET/CT 3 months after initial treatment followed by direct laryngoscopy with biopsy of the identified lesions has the potential to reduce the number of unnecessary laryngoscopies.

Radiobiological comparison of flattening filter (FF) and flattening filter-free (FFF) beam in rat laryngeal tissue.

PURPOSE: The purpose of this study is to investigate the radioprotective effect of melatonin by analyzing histopathological changes and serum biochemical levels on experimental rat models exposed to flattening filter (FF) and flattening filter-free (FFF) beam. MATERIALS AND METHODS: Forty-eight healthy adult Sprague Dawley rats were randomly divided into six groups. The control (Group 1) was given no treatment, the melatonin (Group 2) was given 10 mg/kg melatonin only, the FF (Group 3) and FFF (Group 5) were given fractionated dose (Total 32 Gy, 5 consecutive days) radiotherapy only, and the FF plus melatonin (Group 4) and FFF plus melatonin (Group 6) were given 10 mg/kg melatonin 15 minutes prior to irradiation. Rats were examined for histopathology and biochemical analysis 10 days after irradiation. RESULTS: When results of FF and FFF radiotherapy only groups are compared to control group, statistically significant difference in histopathological and biochemical parameters are observed; however, melatonin administration in radiotherapy plus melatonin groups improved these parameters (p <.05). In addition, there was no statistically significant difference between FF and FFF beams (p > .05). CONCLUSIONS: The effect of low- and high-dose beams on the rat larynx and serum samples were investigated histopathologically and biochemically for the first time. We observed that melatonin supplemented before FF and FFF radiotherapy protected early period radiotherapy-induced laryngeal mucosal damage. Since the radiobiological results of FF and FFF beams are similar, FFF beams can be safely applied in laryngeal irradiation. However, more experimental rat and clinical studies are needed to clarify the radiobiological uncertainy concerning dose rate on cancerous and healthy tissue.

Solitary extramedullary plasmacytoma of the larynx: a rare cause of dysphonia.

Solitary extramedullary plasmacytoma (SEP) of the larynx is a rare haematological malignancy and an infrequent cause of persisting dysphonia. We present the case of a 54-year-old woman with a long-standing history of dysphonia. While clinical examination showed a rather inconspicuous prominent right vestibular fold, an MRI revealed a laryngeal mass with erosion of the thyroid cartilage. A biopsy taken during rigid endoscopy demonstrated plasma cell infiltration with light chain restriction amidst amyloid deposits. After exclusion of systemic involvement, the diagnosis of an SEP of the larynx with secondary amyloidosis was made. The patient received primary radiation therapy. Another biopsy taken 3 months after the end of therapy did not show any signs of ongoing neoplastic plasma cell disease. The patient was therefore considered to be in remission. She is currently receiving regular follow-up and has not shown signs of persistent or progressive disease for the past 18 months.

Evaluating different radiotherapy treatment plans, in terms of critical organ scoring index, conformity index, tumor control probability, and normal tissue complication probability calculations in early glottic larynx carcinoma.

PURPOSE: In this study, it is aimed to compare three different radiotherapy treatment planning techniques in terms of critical organ scoring index (COSI), two different conformity index (CI), tumor control probability (TCP), and normal tissue complication probability (NTCP) calculations in early (T1) glottic larynx carcinoma (T1GL). Furthermore, it is aimed to investigate these parameters compliance with dose-volume histograms (DVH) parameters. MATERIALS AND METHODS: Ten T1GL patients were immobilized in a supine position with a head and neck thermoplastic mask. Treatment plans were created with opposed lateral fields (OLAFs) and intensity-modulated radiation therapy (IMRT) techniques with a total dose of 66 Gy in 33 fraction with 2 Gy/day. IMRT fields were selected as five fields (5IMRT) and seven fields (7IMRT). Dosimetric evaluation of three different treatment plans for T1GL carcinoma was performed in two consequential steps. First step was the assessment of planning target volume (PTV), all organs at risks (OARs), and normal tissue (NT) dose calculations according to given dose constraint directions and comparing the plans via DVH. In the second step, for PTV, the compatibility of DVH data with CIs-TCP was investigated where COSI-NTCP was compared with DVH for OARs. The DVH data were considered as reference in all evaluations. RESULTS: The CIRTOG mean values were significantly closer to 1 with IMRT plans when compared to OLAF plans (P = 0.005). The CIPADDICK mean values revealed that OLAF plans were significantly worse than IMRT plans (P = 0.005). No statistically significant difference was found between all three plans in terms of homogeneity index mean values (P = 0.076). The calculated mean TCP values were significantly better for 7IMRT plans when compared to OLAF and 5IMRT plans (P = 0.007 and P = 0.017, respectively). Both NTCP and COSI evaluations, which is compatible with DVH, significantly favored OLAF plan for spinal cord and 7IMRT for thyroid gland. The COSI evaluations, which are compatible with DVH, significantly favored 7IMRT plan for carotid arteries and 5IMRT plan for NT. CONCLUSION: Our results demonstrated that CIPADDICK-TCP calculations for PTV and COSI-NTCP calculations for OARs were compatible with DVH in T1 GL plans. Therefore, we suggest such parameters as valuable tools for choosing the feasible one among multiple plans and even with different treatment machines.

Laser induced autofluorescence lifetime to identify larynx squamous cell carcinoma: Short series ex vivo study.

Laser induced autofluorescence (LIAF) lifetime is useful to distinguish between normal laryngeal tissues and squamous cell carcinoma (SCC) based on variations of their biochemical composition and structure alterations. LIAF was collected from samples constituted by pairs of normal and malignant tissue, which were excised from three patients. Exclusion criteria for samples harvest were: (i) macroscopic changes of normal vocal cord observed during surgery; (ii) previous surgical intervention on vocal cord, (iii) patients treated only with chemotherapy or radiotherapy for carcinoma. Inclusion conditions: men, aged 57-68, non-smokers. A pulsed laser diode excited LIAF at 375 nm and 31 MHz repetition rate; beam full-time width at half-maximum was 87 ps at an average power of 0.49 mW. Mean LIAF lifetime for normal tissues was (3.75 ± 0.49) ns and for malignant (4.37 ± 0.85) ns: it is longer in malignant than in normal tissue. Variance analysis made with Fisher's test has shown no significant difference between patients for normal tissues; the same was true for malignant. Though, when malignant tissue was compared to normal for the same patients as well as between patients, a significant difference (significance level of 5%) was evidenced. Time-resolved LIAF may allow better differentiation between normal and malignant tissues in patients diagnosed with larynx SCC.

Association of clinical factors with survival outcomes in laryngeal squamous cell carcinoma (LSCC).

AIM: Treatment strategies in laryngeal squamous cell cancer (LSCC) straddle the need for long term survival and tumor control as well as preservation of laryngeal function as far as possible. We sought to identify prognostic factors affecting LSCC outcomes in our population. METHODS: Clinical characteristics, treatments and survival outcomes of patients with LSCC were analysed. Baseline comorbidity data was collected and age-adjusted Charlson Comorbidity Index (aCCI) was calculated. Outcomes of overall survival (OS), progression-free survival (PFS) and laryngectomy-free survival (LFS) were evaluated. RESULTS: Two hundred and fifteen patients were included, 170 (79%) underwent primary radiation/ chemoradiation and the remainder upfront surgery with adjuvant therapy where indicated. The majority of patients were male, Chinese and current/ex-smokers. Presence of comorbidity was common with median aCCI of 3. Median OS was 5.8 years. On multivariable analyses, high aCCI and advanced nodal status were associated with inferior OS (HR 1.24 per one point increase in aCCI, P<0.001 and HR 3.52; p<0.001 respectively), inferior PFS (HR 1.14; p = 0.007 and HR 3.23; p<0.001 respectively) and poorer LFS (HR 1.19; p = 0.001 and HR 2.95; p<0.001 respectively). Higher tumor (T) stage was associated with inferior OS and LFS (HR 1.61; p = 0.02 and HR 1.91; p = 0.01 respectively). CONCLUSION: In our Asian population, the presence of comorbidities and high nodal status were associated with inferior OS, PFS and LFS whilst high T stage was associated with inferior LFS and OS.

Factors affecting voice quality in early glottic cancer before and after radiotherapy.

Background Radiotherapy (RT) is a successful mode of treatment for early glottic cancer. The aim of the study was to assess voice quality both before and 3 months after successful RT using multimodal methods while also identifying the factors affecting it. Patients and methods In 50 patients with T1 glottic carcinoma, the subjective (patients' assessment of voice quality [VAS], Voice Handicap Index [VHI] questionnaire, phoniatricians' assessment using the grade/roughness/ breathiness [GRB] scale), and objective assessments (fundamental laryngeal frequency [F0], jitter, shimmer, maximum phonation time [MPT]) of voice quality were performed before RT and 3 months post-RT. The data on gender, age, extent of the tumors, biopsy types, smoking, local findings, and RT were obtained from the medical documentation. Results Three months after the treatment, VAS, VHI, G and R scores, F0, and MPT significantly improved in comparison with their assessment prior to treatment. Before the treatment, the involvement of the anterior commissure significantly deteriorated jitter (p = 0.044) and the involvement of both vocal folds deteriorated jitter (p = 0.003) and shimmer (p = 0.007). After the RT, F0 was significantly higher in the patients with repeated biopsy than in the others (p = 0.047). In patients with post-RT changes, the B score was significantly higher than in those without post-RT changes (p = 0.029). Conclusions Voice quality already significantly improved three months after the treatment of glottic cancer. The main reason for the decreased voice quality prior to treatment is the tumor's extent. Post-RT laryngeal changes and repeated biopsies caused more scarring on vocal folds adversely influencing voice quality after the treatment.

Harmonization of proton treatment planning for head and neck cancer using pencil beam scanning: first report of the IPACS collaboration group.

Background and purpose: A collaborative network between proton therapy (PT) centres in Trento in Italy, Poland, Austria, Czech Republic and Sweden (IPACS) was founded to implement trials and harmonize PT. This is the first report of IPACS with the aim to show the level of harmonization that can be achieved for proton therapy planning of head and neck (sino-nasal) cancer.Methods: CT-data sets of five patients were included. During several face-to-face and online meetings, a common treatment planning protocol was developed. Each centre used its own treatment planning system (TPS) and planning approach with some restrictions specified in the treatment planning protocol. In addition, volumetric modulated arc therapy (VMAT) photon plans were created.Results: For CTV1, the average Dmedian was 59.3 ± 2.4 Gy(RBE) for protons and 58.8 ± 2.0 Gy(RBE) for VMAT (aim was 56 Gy(RBE)). For CTV2, the average Dmedian was 71.2 ± 1.0 Gy(RBE) for protons and 70.6 ± 0.4 Gy(RBE) for VMAT (aim was 70 Gy(RBE)). The average D2% for the spinal cord was 25.1 ± 8.5 Gy(RBE) for protons and 47.6 ± 1.4 Gy(RBE) for VMAT. The average D2% for chiasm was 46.5 ± 4.4 Gy(RBE) for protons and 50.8 ± 1.4 Gy(RBE) for VMAT, respectively. Robust evaluation was performed and showed the least robust plans for plans with a low number of beams.Discussion: In conclusion, several influences on harmonization were identified: adherence/interpretation to/of the protocol, available technology, experience in treatment planning and use of different beam arrangements. In future, all OARs that should be included in the optimization need to be specified in order to further harmonize treatment planning.

Induction chemotherapy in head and neck cancers: Results and controversies.

Standard treatment for locally advanced head and neck squamous cell carcinoma (LAHNSCC) consists mainly of concurrent chemoradiation (CCR) but induction chemotherapy (IC) by docetaxel-cisplatin-fluorouracil (TPF), followed by CCR, is a strong option. Comparative trials suggest that IC and CCR are equivalent, and some trials suggest superiority of IC, whereas none shows inferiority. IC might have less interest in oropharyngeal cancer (more often linked to HPV infection). When functional laryngeal preservation is the patient's priority, essays strongly suggest that IC is the best treatment. There is little data about a less toxic regimen of IC, but several schemes are promising and need to be developed. An early selection of responders to IC by metabolic imaging must be considered. Intensification attempts with cetuximab were too toxic and unsafe, but trials with immunotherapy are ongoing to enhance TPF efficacy. After IC, CCR either with cetuximab or cisplatin seems to be equally effective.