Better preservation of erectile function in localized prostate cancer patients with modern proton therapy: Is it cost-effective?

BACKGROUND: Stereotactic body radiation therapy (SBRT) has gradually been recognized as favorable curative treatment for localized prostate cancer (PC). However, the high rate of erectile dysfunction (ED) after traditional photon-based SBRT remains an ongoing challenge that greatly impacts the quality of life of PC survivors. Modern proton therapy allows higher conformal SBRT delivery and has the potential to reduce ED occurrence but its cost-effectiveness remains uninvestigated. METHODS: A Markov decision model was designed to evaluate the cost-effectiveness of proton SBRT versus photon SBRT in reducing irradiation-related ED. Base-case evaluation was performed on a 66-year-old (median age of PC) localized PC patient with normal pretreatment erectile function. Further, stratified analyses were performed for different age groups (50, 55, 60, 65, 70, and 75 years) and threshold analyses were conducted to estimate cost-effective scenarios. A Chinese societal willingness-to-pay (WTP) threshold (37,653 US dollars [$])/quality-adjusted life-year [QALY]) was adopted. RESULTS: For the base case, protons provided an additional 0.152 QALY at an additional cost of $7233.4, and the incremental cost-effectiveness ratio was $47,456.5/QALY. Protons was cost-effective for patients ≤62-year-old at the WTP of China (≤66-year-old at a WTP of $50,000/QALY; ≤73-year-old at a WTP of $100,000/QALY). For patients at median age, once the current proton cost ($18,000) was reduced to ≤$16,505.7 or the patient had a life expectancy ≥88 years, protons were cost-effective at the WTP of China. CONCLUSIONS: Upon assumption-based modeling, the results of current study support the use of proton SBRT in younger localized PC patients who are previously potent, for better preservation of erectile function. The findings await further validation using data from future comparative clinical trials.

Therapeutic strategies, oncologic and swallowing outcomes and their predictive factors in patients with locally advanced hypopharyngeal cancer.

INTRODUCTION: Hypopharyngeal cancer (HC) is an aggressive and life-threatening malignancy that requires a complex multimodal treatment. The aims of the present study were to analyze, in locally advanced HC patients, the oncologic and swallowing outcomes and their predictive factors according to the therapeutic strategy. METHODS: All patients with locally advanced HC (T3/T4, N0-3, M0) treated at our institution between 2000 and 2020 were included in this retrospective study. Patients were classified in 3 groups according to the therapeutic strategy: primary radical surgery (RS), induction chemotherapy (ICT) or definitive (chemo)-radiation therapy ((C)RT). Predictive factors of oncologic outcomes (overall, cause-specific and recurrence-free survival: OS, CSS and RFS) and swallowing outcome (dysphagia outcome and severity scale: DOSS) were investigated in univariate and multivariate analysis. RESULTS: A total of 217 patients were included in this study (RS: 40; ICT: 106; (C)RT: 71). 5-year OS, CSS and RFS rates were 36, 38 and 32%, respectively. ICT was associated with improved oncologic and swallowing outcomes in univariate analysis. After multivariate analysis, patient age ≥ 70 years (p = 0.0002) was the only factor significantly associated with a worse OS, whereas patient age ≥ 70 years (p = 0.002) and N stage ≥ 2 (p = 0.01) were significantly associated with a worse CSS. Comorbidity level (KFI ≥ 2; p = 0.01) and N stage (≥ 2; p = 0.02) were significantly associated with worse swallowing outcomes. CONCLUSION: In selected locally advanced HC patients, an ICT-based therapeutic strategy offers acceptable oncologic and functional outcomes. Patient age, N stage and comorbidity level are the main determinants of oncologic and functional outcomes.

Optimizing oropharyngeal cancer management by using proton beam therapy: trends of cost-effectiveness.

BACKGROUND: Proton beam therapy (PBT) is a new-emerging cancer treatment in China but its treatment costs are high and not yet covered by Chinese public medical insurance. The advanced form of PBT, intensity-modulated proton radiation therapy (IMPT), has been confirmed to reduce normal tissue complication probability (NTCP) as compared to conventional intensity-modulated photon-radiation therapy (IMRT) in patients with oropharyngeal cancer (OPC). Herein, we evaluated the cost-effectiveness and applicability of IMPT versus IMRT for OPC patients in China, aiming at guiding the proper use of PBT. METHODS: A 7-state Markov model was designed for analysis. Base-case evaluation was performed on a 56-year-old (median age of OPC in China) patient under the assumption that IMPT could provide a 25% NTCP-reduction in long-term symptomatic dysphagia and xerostomia. Model robustness was examined using probabilistic sensitivity analysis, cohort analysis, and tornado diagram. One-way sensitivity analyses were conducted to identify the cost-effective scenarios. IMPT was considered as cost-effective if the incremental cost-effectiveness ratio (ICER) was below the societal willingness-to-pay (WTP) threshold. RESULTS: Compared with IMRT, IMPT provided an extra 0.205 quality-adjusted life-year (QALY) at an additional cost of 34,926.6 US dollars ($), and had an ICER of $170,082.4/ QALY for the base case. At the current WTP of China ($33,558 / QALY) and a current IMPT treatment costs of $50,000, IMPT should provide a minimum NTCP-reduction of 47.5, 50.8, 55.6, 63.3 and 77.2% to be considered cost-effective for patient age levels of 10, 20, 30, 40 and 50-year-old, respectively. For patients at the median age level, reducing the current IMPT costs ($50,000) to a $30,000 level would make the minimum NTCP-reduction threshold for "cost-effective" decrease from 91.4 to 44.6%, at the current WTP of China (from 69.0 to 33.5%, at a WTP of $50,000 / QALY; and from 39.7 to 19.1%, at a WTP of $100,000 / QALY). CONCLUSIONS: Cost-effective scenarios of PBT exist in Chinese OPC patients at the current WTP of China. Considering a potential upcoming increase in PBT use in China, such cost-effective scenarios may further expand if a decrease of proton treatment costs occurs or an increase of WTP level.

Correlations between long-term quality of life and patient needs and concerns following head and neck cancer treatment and the impact of psychological distress. A multicentric cross-sectional study.

OBJECTIVES: To assess patient needs and concerns after head and neck squamous cell carcinoma (HNSCC) treatment and their possible correlations with long-term quality of life (QoL) and to examine the potential impact of psychological distress on these results. METHODS: Alive and disease-free HNSCC patients at least 1 year after treatment were enrolled in this cross-sectional multicentric study and completed the EORTC QLQ-C30 and H&N35 QoL questionnaires, the head and neck cancer-specific patient concerns inventory (PCI-HN) questionnaire and the hospital anxiety and depression scale (HADS). Correlations between QoL outcomes and patient needs and concerns were investigated using Spearman's correlation tests. RESULTS: Seventy-two patients were enrolled in the study. Fear of cancer recurrence was the main patient concern followed by dental, salivary, fatigue, speech, and eating problems. The leading patient needs in terms of consultation were to be referred to the surgeon, the speech, and swallow therapist and the oral rehabilitation team. The number of patient concerns correlated negatively (r < .40) with functioning scales score and positively (r > .40) with general and head and neck symptoms. Psychological distress was the main determinant of QoL outcomes (p < .0001). We found a significant impact of gender (p = .002) on the number of patient concerns, and of patient age (p = .003) on the number of staff members selected by patients. CONCLUSION: Identification of patient needs and concerns along with multidisciplinary management of persistent symptoms and psychological distress seem essential steps towards improving QoL of HNSCC patients.

Cost-effectiveness analysis of proton beam therapy for treatment decision making in paranasal sinus and nasal cavity cancers in China.

BACKGROUND: Cost-effectiveness is a pivotal consideration for clinical decision making of high-tech cancer treatment in developing countries. Intensity-modulated proton radiation therapy (IMPT, the advanced form of proton beam therapy) has been found to improve the prognosis of the patients with paranasal sinus and nasal cavity cancers compared with intensity-modulated photon-radiation therapy (IMRT). However, the cost-effectiveness of IMPT has not yet been fully evaluated. This study aimed at evaluating the cost-effectiveness of IMPT versus IMRT for treatment decision making of paranasal sinus and nasal cavity cancers in Chinese settings. METHODS: A 3-state Markov model was designed for cost-effectiveness analysis. A base case evaluation was performed on a patient of 47-year-old (median age of patients with paranasal sinus and nasal cavity cancers in China). Model robustness was examined by probabilistic sensitivity analysis, Markov cohort analysis and Tornado diagram. Cost-effective scenarios of IMPT were further identified by one-way sensitivity analyses and stratified analyses were performed for different age levels. The outcome measure of the model was the incremental cost-effectiveness ratio (ICER). A strategy was defined as cost-effective if the ICER was below the societal willingness-to-pay (WTP) threshold of China (30,828 US dollars ($) / quality-adjusted life year (QALY)). RESULTS: IMPT was identified as being cost-effective for the base case at the WTP of China, providing an extra 1.65 QALYs at an additional cost of $38,928.7 compared with IMRT, and had an ICER of $23,611.2 / QALY. Of note, cost-effective scenarios of IMPT only existed in the following independent conditions: probability of IMPT eradicating cancer ≥0.867; probability of IMRT eradicating cancer ≤0.764; or cost of IMPT ≤ $52,163.9. Stratified analyses for different age levels demonstrated that IMPT was more cost-effective in younger patients than older patients, and was cost-effective only in patients ≤56-year-old. CONCLUSIONS: Despite initially regarded as bearing high treatment cost, IMPT could still be cost-effective for patients with paranasal sinus and nasal cavity cancers in China. The tumor control superiority of IMPT over IMRT and the patient's age should be the principal considerations for clinical decision of prescribing this new irradiation technique.

Evaluation of the information given to patients undergoing total pharyngolaryngectomy and quality of life: a prospective multicentric study.

BACKGROUND: Providing cancer patients with adequate information is essential to their confidence and satisfaction regarding medical care. The aims of this study were to evaluate the information given to patients undergoing total pharyngolaryngectomy (TPL) as well as the evolution and predictors of patient quality of life (QoL). METHODS: We conducted a prospective multicentric study on patients undergoing TPL for a locally advanced laryngeal/hypopharyngeal cancer. All patients completed the EORTC QLQ-INFO25, QLQ-C30, and QLQ-H&N35 questionnaires, before and after surgery. RESULTS: This study enrolled 46 patients. Between the pre- and post-therapeutic periods, we observed no significant changes in the global QLQ-INFO25 and QLQ-C30 scores. However, we found a significant deterioration in 4 QLQ-INFO25 scales/items and in social functioning, as well as an increase of sense, speech, and social contact problems. N-stage and professional activity were significant predictors of preoperative QLQ-INFO25 scores. Younger age was significantly associated with financial difficulties, whereas professional activity and lower education level were significant predictors of xerostomia and swallowing problems, respectively. CONCLUSION: In patients undergoing TPL, we observed significant changes in QLQ-INFO25 scores between the pre- and post-treatment periods and, particularly, a deterioration of patient satisfaction with the information received. Several clinical factors were identified as significant predictors of QLQ-INFO25 and QoL scores.

Multimodal Therapy of Squamous Cell Carcinoma of the Anus With Distant Metastasis: A Single-Institution Experience.

BACKGROUND: Because of the rarity of the condition, studies concerning the management of patients with squamous cell carcinoma of the anus with distant metastasis are scarce. The available studies indicate poor outcomes with exclusive chemotherapy. OBJECTIVE: Our aim was to evaluate the impact of multidisciplinary treatment on overall survival among patients presenting with metastatic squamous cell carcinoma of the anus. DESIGN: This was a retrospective study. SETTINGS: The study was conducted at a single French institution between 2000 and 2014. PATIENTS: Consecutive patients with histologically proven, newly diagnosed, or recurrent metastatic squamous cell carcinoma of the anus were included. INTERVENTIONS: Study interventions included multimodal therapy combining systemic chemotherapy and local ablative treatment to remove all metastases through surgery, radiofrequency ablation, or radiotherapy. MAIN OUTCOME MEASURES: The primary outcome measure was overall survival. RESULTS: Fifty patients (median age, 62 years; men/women: 8/42) fulfilled the inclusion criteria, and 39 were available for Response Evaluation Criteria in Solid Tumors. Forty had metastatic relapse after previous treatment of localized disease, and 10 presented with synchronous metastasis. P16 status was not available. Patients received at least 1 chemotherapy regimen, including 5-fluorouracil-mitomycin C (n = 22), cisplatin-5-fluorouracil (n = 20), or 5-fluorouracil alone (n = 3). Thirteen also had surgical metastasectomy, 11 had radiotherapy, and 6 had radiofrequency ablation. Median overall survival was 20.0 months (95% CI, 18.2-21.8 mo), and median time to failure of strategy was 6.0 months (95% CI, 2.9-9.1 mo). Overall response rate was 56% (95% CI, 40%-73%). Outcomes from the 5-fluorouracil-mitomycin C and cisplatin regimens did not statistically differ. Patients treated with multimodal therapy had a median overall survival of 22.0 months (95% CI, 15.3-28.6 mo) versus 13.0 months (95% CI, 9.5-16.5 mo; p = 0.002). Median time to failure of strategy was 10.0 months (95% CI, 4.2-15.7 mo) versus 5.0 months (95% CI, 2.8-7.2; p = 0.007). After 2 years, 40% of patients with multimodal treatment and 20% of those without ablative treatment were alive. LIMITATIONS: This study is limited by its retrospective design and modest sample size. CONCLUSIONS: Stage IV squamous cell carcinoma of the anus outcomes are poor, but first-line chemotherapy can enable good response rates. Other treatment modalities, including surgery, radiotherapy, and thermoablation, should be considered, because they may provide a survival advantage. See Video Abstract at http://links.lww.com/DCR/A336.

Radiotherapy for elderly patients and cetuximab, a monocentric study.

Concomitant radiotherapy and cetuximab association has shown superiority to exclusive radiotherapy for head and neck cancers. Data on this association are scarce for the elderly population despite its rising incidence. A retrospective monocentric data collection was performed in the Antoine Lacassagne Cancer Center in France. Inclusion criteria were: age >70 years at time of diagnosis, histologically proven head and neck epidermoid carcinoma, treated with radiotherapy combined with cetuximab. Thirty-five patients were included between 2008 and 2012. Median follow-up was 22 months. Median age was 74 years (70-86). Median performance status was 1 (0-2). Female/male sex ratio was 0.34. Tumor sites were: oropharynx (57.1 %), larynx (20 %), hypopharynx (14.3 %), oral cavity (2.9 %), nasopharynx (2.9 %), and lymph node with unknown primary (2.9 %). Using TNM classification, tumors were: T1 (5.9 %), T2 (35.3 %), T3 (35.3 %), T4 (22.9 %), N0 (28.6 %), N1 (8.6 %), N2 (48.6 %), and N3 (14.3 %). Median radiotherapy dose was 70 (60-70). RT was interrupted in 94 % of patients and the dose of cetuximab was reduced in 29 %. Median survivals were, respectively: 49 months for overall survival (standard error (SE) = 8) and 32 months for relapse-free survival (SE = 10). Two-year local-regional relapse and metastatic relapse-free survivals were, respectively, 59 % (SE = 10) and 74 % (SE = 10). Concomitant radiotherapy and cetuximab seem to be an effective therapy in the elderly population with encouraging results similar to the literature concerning its efficacy and toxicity. This treatment should be considered for patients >70 years.

Primary radical ablative surgery and fibula free-flap reconstruction for T4 oral cavity squamous cell carcinoma with mandibular invasion: oncologic and functional results and their predictive factors.

The aims of this study were to evaluate clinical outcomes and to determine their predictive factors in patients with oral cavity squamous cell carcinoma (OCSCC) invading the mandibular bone (T4) who underwent primary radical surgery and fibula free-flap reconstruction. Between 2001 and 2013, all patients who underwent primary surgery and mandibular fibula free-flap reconstruction for OCSCC were enrolled in this retrospective study. Predictive factors of oncologic and functional outcomes were assessed in univariate and multivariate analysis. 77 patients (55 men and 22 women, mean age 62 ± 10.6 years) were enrolled in this study. Free-flap failure and local and general complication rates were 9, 31, and 22 %, respectively. In multivariate analysis, ASA score (p = 0.002), pathologic N-stage (p = 0.01), and close surgical margins (p = 0.03) were independent predictors of overall survival. Six months after therapy, oral diet, speech intelligibility, and mouth opening functions were normal or slightly impaired in, respectively, 79, 88, and 83 % of patients. 6.5 % of patients remaining dependent on enteral nutrition 6 months after therapy. With acceptable postoperative outcomes and satisfactory oncologic and functional results, segmental mandibulectomy with fibula free-flap reconstruction should be considered the gold standard primary treatment for patients with OCSCC invading mandible bone. Oncologic outcomes are dependent on three main factors: ASA score, pathologic N-stage, and surgical margin status.

Induction chemotherapy-based larynx preservation program for locally advanced hypopharyngeal cancer: oncologic and functional outcomes and prognostic factors.

To evaluate oncologic and functional outcomes and prognostic factors in patients with locally advanced hypopharyngeal cancer included in an induction chemotherapy (ICT)-based larynx preservation program in daily clinical practice. All patients with locally advanced (T3/4, N0-3, M0) hypopharyngeal squamous cell carcinoma, technically suitable for total pharyngo-laryngectomy, treated by docetaxel (75 mg/m(2), day 1), cisplatin (75 mg/m(2), day 1) and 5-fluorouracil (750 mg/m(2)/day, day 1-5) (TPF)-ICT (2-3 cycles) for larynx preservation at our institution between 2004 and 2013, were included in this retrospective study. Prognostic factors of oncologic (overall, cause-specific and recurrence-free survival: OS, SS and RFS) and functional (dysphagia outcome and severity scale, permanent enteral nutrition, larynx preservation) outcomes were assessed in univariate and multivariate analyses. A total of 53 patients (42 men and 11 women, mean age 58.6 ± 8.2 years) were included in this study. Grade 3-4 toxicities were experienced by 17 (32 %) patients during ICT. The rate of poor response (response <50 % without larynx remobilization) to ICT was 10 %. At 5 years, OS, SS and RFS rates were 56, 60 and 54 %, respectively. Four patients required definitive enteral nutrition (permanent enteral tube feeding). The rate of patients alive, disease-free and with a functional larynx at 2 years was 58 %. T4 tumor stage (p = 0.005) and response to ICT <50 % (p = 0.02) were independent prognostic factors of OS. Response to ICT was significantly associated with the risk of permanent enteral nutrition (p = 0.04) and larynx preservation (p = 0.01). In daily clinical practice, a TPF-ICT-based larynx preservation protocol can be used in patients with locally advanced hypopharyngeal cancer with satisfactory results in terms of tolerance, efficacy and oncologic and functional outcomes.

Nutritional status and feeding-tube placement in patients with locally advanced hypopharyngeal cancer included in an induction chemotherapy-based larynx preservation program.

The objective of the study is to evaluate the nutritional status and determine its impact on clinical outcomes in patients with locally advanced hypopharyngeal cancer included in an induction chemotherapy (ICT)-based larynx preservation program without prophylactic feeding-tube placement. All patients with locally advanced (T3/4, N0-3, M0) hypopharyngeal squamous cell carcinoma, technically suitable for total pharyngolaryngectomy, treated by docetaxel, cisplatin and 5-fluorouracil (TPF)-ICT for larynx preservation at our institution between 2004 and 2013, were included in this retrospective study. Patients' nutritional status was closely monitored. Enteral nutrition was used if and when a patient was unable to sustain per-oral nutrition and hydration. The impact of nutritional status on clinical outcomes was investigated in univariate and multivariate analysis. A total of 53 patients (42 men and 11 women, mean age = 58.6 ± 8.2 years) were included in this study. Six (11.3 %) patients had lost more than 10 % of their usual body weight before therapy. Compared with patients' usual weight, the mean maximum patient weight loss during therapeutic management was 8.7 ± 4.5 kg. Enteral nutrition was required in 17 patients (32 %). We found no influence of the tested nutritional status-related factors on response to ICT, toxicity of ICT, overall, cause-specific and recurrence-free survival, and on post-therapeutic swallowing outcome. Maximum weight loss was significantly associated with a higher risk of enteral tube feeding during therapy (p = 0.03) and of complications (grade ≥3, p = 0.006) during RT. Without prophylactic feeding-tube placement, approximately one-third of the patients required enteral nutrition. There was no significant impact of nutritional status on oncologic or functional outcomes.

[Peri-operative treatments for rectal cancer]. / Traitements péri-opératoires du cancer du rectum.

Depending on its location or stage, rectal cancer may differ significantly. Before any treatment decision a careful work up is mandatory relying mainly on endoscopy and imaging (MRI). Surgery according to the TME principle is the cornerstone of treatment. Most of the time surgery is associated with external beam radiotherapy often combined with concurrent chemotherapy (capecitabine) according to the neoadjuvant regimen CAP 50 (5 weeks long). It is sometimes possible to escalate safely the dose of irradiation using contact X-ray brachytherapy 50 Kv or Iridium 192 interstitial brachytherapy. Adjuvant chemotherapy may be given in case of pejorative pathological findings but its benefit is not yet proven in contrast with colon cancer. Local recurrences are becoming unusual as is permanent APE surgery with permanent stoma. To reduce the risk of distant metastasis clinical trials are testing first line chemotherapy in T3-4 lesions. For early stage (T2-"small" T3) clinical trials try to achieve organ preservation. Intensification of CAP 50 either with more chemotherapy or radiation dose escalation using contact X-ray aim at achieving a clinical complete response followed by local excision or close surveillance.

Long-term quality of life and its predictive factors after oncologic surgery and microvascular reconstruction in patients with oral or oropharyngeal cancer.

The aims of this study were to evaluate long-term quality of life (QoL) and to determine its predictive factors after oncologic surgery and free flap reconstruction in patients with oral or oropharyngeal cancer. Patients treated at our institution between 2000 and 2009, who are alive and disease-free at least 1 year after therapy, completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire and the specific H&N35 module. Eighty patients were included in our study. Global QoL score was 69.3 ± 22.7%. Global QoL and general symptoms were correlated with T stage, whereas head and neck symptoms were correlated with T stage and tumor involvement of the tongue base. Emotional and social functioning scales, and resumption of professional activity were significantly associated with global QoL. In conclusion, T stage, tumor involvement of the tongue base, professional status and emotional and social functions were the main determinants of QoL in our study.

Cost-effectiveness of weekly adaptive radiotherapy versus standard IMRT in head and neck cancer alongside the ARTIX trial.

BACKGROUND AND PURPOSE: We performed a cost-effectiveness analysis (CEA) comparing an adaptive radiotherapy (ART) strategy, based on weekly replanning, aiming to correct the parotid gland overdose during treatment and expecting therefore to decrease xerostomia, when compared to a standard IMRT. MATERIALS AND METHODS: We conducted the ARTIX trial, a randomized, parallel-group, multicentric study comparing a systematic weekly replanning ART to a standard IMRT. The primary endpoint was the frequency of xerostomia at 12 months, measured by stimulating salivary flow with paraffin. The CEA was designed alongside the ARTIX trial which was linked to the French national health data system (SNDS). For each patient, healthcare consumptions and costs were provided by the SNDS. The reference case analysis was based on the primary endpoint of the trial. Sensitivity and scenario analyses were performed. RESULTS: Of the 129 patients randomly assigned between 2013 and 2018, only 2 records were not linked to the SNDS, which provides a linkage proportion of 98.4%. All of the other 127 records were linked with good to very good robustness. On the intent-to-treat population at 12 months, mean total costs per patient were €41,564 (SD 23,624) and €33,063 (SD 16,886) for ART and standard IMRT arms, respectively (p = 0.033). Incremental cost effectiveness ratio (ICER) was €162,444 per xerostomia avoided. At 24 months, ICER was €194,521 per xerostomia avoided. For both progression-free and overall survival, ART was dominated by standard IMRT. CONCLUSION: The ART strategy was deemed to be not cost-effective compared with standard IMRT for patients with locally advanced oropharyngeal cancer.

Predictive factors for early and late local toxicities in anal cancer treated by radiotherapy in combination with or without chemotherapy.

BACKGROUND: The treatment of anal cancer is based on concomitant radiotherapy and chemotherapy and is associated with a nonnegligible rate of local severe toxicities that can strongly impair the quality of life. OBJECTIVE: A retrospective analysis was performed to screen the following factors as potential predictive factors for local skin and digestive toxicities, and as potential prognostic factors for cumulative colostomy incidence: sex, age, tumor size, clinical T and N stage, circumferential extension, invasion of anal margin, HIV status, type of chemotherapy, and type of radiotherapy and dose delivered. METHODS: One hundred five patients in our database treated between January 2000 and February 2010 met the eligibility criteria. RESULTS: Median follow-up was 54.1 months (range, 1-133). Early and late severe local toxicities occurred in 33 patients (31.4%) and 18 patients (17.1%). The 5-year cumulative rate of colostomy was 26.6%. Predictive factors for local severe early toxicities were as follows: clinical stage III/IV (p = 0.01), no brachytherapy boost (p = 0.003), and use of chemotherapy (p = 0.01). Only brachytherapy retained its independence in multivariate analysis (OR = 4.8 (1.4-16.3), p = 0.01). Human immunodeficiency virus positivity (p = 0.04) was the only predictive factor for late toxicities in univariate analysis; it was linked independently to the occurrence of ulcer (OR = 0.1 (0.01-0.66), p = 0.01). Tumor size ≥4 cm (p < 0.001) and occurrence of grade 2 to 3 ulcers (p < 0.001) were correlated with greater cumulative colostomy incidence. CONCLUSIONS: In this cohort, nonuse of brachytherapy was an independent predictive factor for local acute toxicity. Human immunodeficiency virus positivity was the only predictive factor for local late toxicities and strongly influenced the onset of ulcer.

Significance of circulating tumor cell detection using the CellSearch system in patients with locally advanced head and neck squamous cell carcinoma.

The objective of this study was to evaluate the potential detection of circulating tumor cells (CTCs) using the CellSearch (CS) Assay™ in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) and then to identify the clinical factors predictive of the presence of CTCs. The presence and number of CTCs were determined using the CS system before treatment, and in 10 healthy individuals (control group). The CS system was able to successfully identify the presence of CTCs in 8 of 49 patients (16 %) before therapy. No CTC was found in the control group. CTCs were detected before therapy in 1 of 19 patients (5 %) with N0 tumor and in 7 of 30 patients (23 %) with N1-2c tumor (p = 0.12; Fisher's exact test). CTCs were identified in a relatively low proportion of patients with locally advanced HNSCC.

Prognostic impact of post-treatment FDG PET/CT in anal canal cancer: A prospective study.

BACKGROUND AND PURPOSE: The aim of our prospective study was to assess the prognostic value of 18F-FDG PET/CT performed two months post treatment for anal canal neoplasm. POPULATION AND METHODS: Consecutive patients with histologically proved anal cancer, with 18F-FDG PET/CT pre and two months post treatment were included. Patients were not previously treated for this neoplasm and then received radiotherapy ± chemotherapy. Clinical and pathologic data were collected and for 18F-FDG PET/CT visual and quantitative analysis (standardized uptake value, metabolic volume) were performed; response was classified according to EORTC and PERCIST criteria. The results were assessed for disease free survival and local recurrence free survival using the log-Rank test RESULTS: From December 2014 to September 2019, 94 consecutive patients were screened and 78 were included in this study. Median follow-up was 51 months. Two months post treatment, 37 patients (47.4%) had a complete radiological response according to both EORTC and PERCIST criteria, 66 patients (84.6%) had a clinical complete response. For disease free survival, the prognostic value of complete response was statistically significant (p=0.02) with 18F-FDG PET/CT and with clinical examination (p<0.001). For local recurrence free survival, the prognostic value with 18F-FDG PET/CT was lower (p=0.04) than clinical examination (p < 0.007). CONCLUSION: While clinical examination remains the gold standard for post treatment evaluation in anal cancer, 18F-FDG PET/CT has a statistically significant prognostic value. These two assessments could be combined to improve early evaluation.

Enteral Nutrition during Radiotherapy for Oropharyngeal Cancers: Prevalence and Prognostic Factors Based on HPV Status (A GETTEC Study).

Nutritional support during radiotherapy is crucial to tolerating and completing oropharyngeal squamous cell carcinoma (OPSCC) treatment. The impact of HPV status on nutritional support is debated. The objective was to evaluate the rate of Reactive Feeding Tube (RFT) use and determine its prognostic factors during definitive radiotherapy for OPSCC. All OPSCC patients treated from 2009 to 2014 were included in this multicentric retrospective study. The impact of tumor p16 status on the risk of RFT was assessed through multivariate analyses. Among the 543 patients, 103 patients required an RFT (19.0%). The use of RFT differed between centers (5% to 32.4%). In multivariate analysis, only tongue base involvement and concurrent chemotherapy were significantly associated with RFT (OR = 2.18 and 3.7, respectively). Tongue base involvement and concomitant chemotherapy were prognostic factors for RFT. HPV status was not a prognostic factor for enteral nutrition during radiotherapy for OPSCC.

Weekly Adaptive Radiotherapy vs Standard Intensity-Modulated Radiotherapy for Improving Salivary Function in Patients With Head and Neck Cancer: A Phase 3 Randomized Clinical Trial.

Importance: Xerostomia is a major toxic effect associated with intensity-modulated radiotherapy (IMRT) for oropharyngeal cancers. Objective: To assess whether adaptive radiotherapy (ART) improves salivary function compared with IMRT in patients with head and neck cancer. Design, Setting, and Participants: This phase 3 randomized clinical trial was conducted in 11 French centers. Patients aged 18 to 75 years with stage III-IVB squamous cell oropharyngeal cancer treated with chemoradiotherapy were enrolled between July 5, 2013, and October 1, 2018. Data were analyzed from November 2021 to May 2022. Interventions: The patients were randomly assigned (1:1) to receive standard IMRT (without replanning) or ART (systematic weekly replanning). Main Outcomes and Measures: The primary end point was the frequency of xerostomia, measured by stimulating salivary flow with paraffin. Secondary end points included salivary gland excretory function measured using technetium-99m pertechnetate scintigraphy, patient-reported outcomes (Eisbruch xerostomia-specific questionnaire and the MD Anderson Symptom Inventory for Head and Neck Cancer questionnaire), early and late toxic effects, disease control, and overall and cancer-specific survival. Results: A total of 132 patients were randomized, and after 1 exclusion in the ART arm, 131 were analyzed: 66 in the ART arm (mean [SD] age at inclusion, 60 [8] years; 57 [86.4%] male) and 65 in the standard IMRT arm (mean [SD] age at inclusion, 60 [8] years; 57 [87.7%] male). The median follow-up was 26.4 months (IQR, 1.2-31.3 months). The mean (SD) salivary flow (paraffin) at 12 months was 630 (450) mg/min in the ART arm and 584 (464) mg/min in the standard arm (P = .64). The mean (SD) excretory function of the parotid gland at 12 months, measured by scintigraphy, improved in the ART arm (48% [17%]) compared with the standard arm (41% [17%]) (P = .02). The 2-year-overall survival was 76.9% (95% CI, 64.7%-85.4%) in both arms. Conclusions and Relevance: This randomized clinical trial did not demonstrate a benefit of ART in decreasing xerostomia compared with standard IMRT. No significant differences were found in secondary end points except for parotid gland excretory function, as assessed by scintigraphy, or in survival rates. Trial Registration: ClinicalTrials.gov Identifier: NCT01874587.

Failure of Initial Curative Treatment for Non-Metastatic Anal Squamous Cell Carcinoma: From Prognostic Factors Analysis to Stratified Treatment.

In squamous cell anal canal neoplasms, persistent disease or recurrence after initial chemoradiotherapy are not the rule, yet their occurrence deserves to be analyzed to better identify prognostics factors. The aim of our study was to describe the patterns of failures of the initial treatment, their subsequent evolution and to identify prognostic factors in these relapsed patients. All patients with non-metastatic anal squamous cell carcinoma initially treated with curative intent at the Centre Antoine Lacassagne between 1999 and 2019, and who presented persistent disease or recurrence were analyzed. The median follow-up was 44 months. Univariate and multivariate analyses were performed to identify prognostic factors. From our database of 528 patients, 77 patients were eligible: 25 with persistent disease and 52 with recurrence after complete response. The median overall survival was 39 months (95% CI: 25.5-52.3 months) from the date of treatment failure. In univariate analysis, prognostic factors were gender, initial lymph node status, type of failure, response to treatment's failure. In multivariate analysis, only female gender remained statistically significant (HR 0.43- P=0.016). 32% of patients with persistent disease had metastatic status. 17.3% and 5.8% of recurrences respectively occurred after three and five years of follow-up. Systematic imaging could be performed after initial treatment because of distant lesions in one third of patients with persistent disease. The follow-up should not be interrupted before five years, given the significant frequency of late recurrences. In multivariate analysis, only female gender was statistically significant. Stratified treatment based on prognostic factors could be envisaged, the details of which remain to be defined.