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.

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.

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.

Association of Oncogenic Mutations in Patients With Advanced Cutaneous Squamous Cell Carcinomas Treated With Cetuximab.

IMPORTANCE: Cetuximab was recently proposed for advanced cutaneous squamous cell carcinomas (cSCC); however, its efficacy is inconsistent and identification of predictive biomarkers for response is necessary. OBJECTIVE: To search for somatic mutations of the HRAS, KRAS, NRAS, BRAF, and EGFR genes in patients with advanced cSCC treated with cetuximab; and to investigate the efficacy and tolerance of cetuximab according to these mutations. DESIGN, SETTING, AND PARTICIPANTS: A multicentric and retrospective study of 31 patients (22 men, 9 women) with histologically confirmed advanced cSCC carried out in 1 department of dermatology and 2 departments of medical oncology in France between January 2008 and December 2014. The median age of participants was 86 years (range, 48-96 years). INTERVENTIONS: Mutational status was determined by pyrosequencing method, allelic discrimination, or Sanger sequencing. Patients were treated by single-agent cetuximab. MAIN OUTCOMES AND MEASURES: The primary end point was the incidence of somatic mutations of the RAS, BRAF, and EGFR genes and association of cetuximab efficacy with these mutations was investigated by using Fisher test. Secondary end points were the disease control rate (DCR) at week 6, the progression free-survival (PFS), overall survival (OS), and safety profile of cetuximab. RESULTS: Thirty-one samples of cSCC from 31 patients were analyzed. Only 2 RAS mutated samples (6.5%) were identified. The first harbored a NRAS point mutation (c.35G>A) in codon 12, resulting in a p.G12D substitution. The second sample presented a HRAS point mutation (c.38G>T) in codon 13, resulting in a p.G13V substitution. No mutation of KRAS, BRAF, and EGFR genes at the investigated loci was found. Two patients with NRAS and HRAS mutations showed a partial and complete response to cetuximab, respectively. The mean duration of follow-up was 19 months. At week 6, the disease control rate was 67.8%. The median OS was 13 months and the median PFS was 9 months. All patients could continue cetuximab treatment without dose reduction. CONCLUSIONS AND RELEVANCE: Even in elderly patients with advanced cSCC, cetuximab was efficacious and well-tolerated. This suggests that cetuximab is certainly warranted in the treatment of advanced cSCC. However, it is also important to identify tumor specific mutations that may determine response to treatment and prognosis for the disease. We have identified here that the incidence of RAS, BRAF, and EGFR mutations is low in cSCC.

Patient satisfaction and acceptance of their totally implanted central venous catheter: a French prospective multicenter study.

INTRODUCTION: Most cancer patients require a totally implanted central venous catheter (TIVAD) for their treatment. In a previous study, we developed and validated a questionnaire dubbed QASICC (Questionnaire for Acceptance of, and Satisfaction with, Implanted Central Venous Catheter) assessing patient satisfaction with, and acceptance of, their TIVAD. In the present study, we conducted a large, prospective, multicenter study in cancer patients aimed to analyze factors that could influence patients' acceptance of, and satisfaction with, their device. METHODS: The QASICC is composed of 22 items assessing 5 dimensions. The construction and validation of the questionnaire was achieved using validated methodology to determine its psychometric characteristics. The questionnaire was submitted to 720 patients in 11 French institutions; 567 answers were analyzed. RESULTS: Younger patients had the most difficulties in coping with their TIVAD, especially regarding daily activities and their body image and private life compared to older patients. Sex was significantly related to patient satisfaction, with worse scores in women. Breast tumor location was also correlated with low TIVAD acceptance. TIVAD on the right side also positively influenced satisfaction and acceptance of the device. CONCLUSIONS: QASICC has proved to be efficient, and to detect known issues regarding daily activities and body image. As our population was mostly composed of women with breast cancer, our results reflect specific aspects of this population. The TIVAD remains generally well-accepted and our questionnaire should help health-care workers to better address the specific needs of their patients based on the answers provided.

Prognostic Value of Bone Marrow Tracer Uptake Pattern in Baseline PET Scans in Hodgkin Lymphoma: Results from an International Collaborative Study.

PET/CT-ascertained bone marrow involvement (BMI) constitutes the single most important reason for upstaging by PET/CT in Hodgkin lymphoma (HL). However, BMI assessment in PET/CT can be challenging. This study analyzed the clinicopathologic correlations and prognostic meaning of different patterns of bone marrow (BM) 18F-FDG uptake in HL. Methods: One hundred eighty newly diagnosed early unfavorable and advanced-stage HL patients, all scanned at baseline and after 2 adriamycin-bleomycin-vinblastine-dacarbazine (ABVD) courses with 18F-FDG PET, enrolled in 2 international studies aimed at assessing the role of interim PET scanning in HL, were retrospectively included. Patients were treated with ABVD × 4-6 cycles and involved-field radiation when needed, and no treatment adaptation on interim PET scanning was allowed. Two masked reviewers independently reported the scans. Results: Thirty-eight patients (21.1%) had focal lesions (fPET+), 10 of them with a single (unifocal) and 28 with multiple (multifocal) BM lesions. Fifty-three patients (29.4%) had pure strong (>liver) diffuse uptake (dPET+) and 89 (48.4%) showed no or faint (≤liver) BM uptake (nPET+). BM biopsy was positive in 6 of 38 patients (15.7%) for fPET+, in 1 of 53 (1.9%) for dPET+, and in 5 of 89 (5.6%) for nPET+ dPET+ was correlated with younger age, higher frequency of bulky disease, lower hemoglobin levels, higher leukocyte counts, and similar diffuse uptake in the spleen. Patients with pure dPET+ had a 3-y progression-free survival identical to patients without any 18F-FDG uptake (82.9% and 82.2%, respectively, P = 0.918). However, patients with fPET+ (either unifocal or multifocal) had a 3-y progression-free survival significantly inferior to patients with dPET+ and nPET+ (66.7% and 82.5%, respectively, P = 0.03). The κ values for interobserver agreement were 0.84 for focal uptake and 0.78 for diffuse uptake. Conclusion: We confirmed that 18F-FDG PET scanning is a reliable tool for BMI assessment in HL, and BM biopsy is no longer needed for routine staging. Moreover, the interobserver agreement for BMI in this study proved excellent and only focal 18F-FDG BM uptake should be considered as a harbinger of HL.

Sunitinib Stimulates Expression of VEGFC by Tumor Cells and Promotes Lymphangiogenesis in Clear Cell Renal Cell Carcinomas.

Sunitinib is an antiangiogenic therapy given as a first-line treatment for renal cell carcinoma (RCC). While treatment improves progression-free survival, most patients relapse. We hypothesized that patient relapse can stem from the development of a lymphatic network driven by the production of the main growth factor for lymphatic endothelial cells, VEGFC. In this study, we found that sunitinib can stimulate vegfc gene transcription and increase VEGFC mRNA half-life. In addition, sunitinib activated p38 MAPK, which resulted in the upregulation/activity of HuR and inactivation of tristetraprolin, two AU-rich element-binding proteins. Sunitinib stimulated a VEGFC-dependent development of lymphatic vessels in experimental tumors. This may explain our findings of increased lymph node invasion and new metastatic sites in 30% of sunitinib-treated patients and increased lymphatic vessels found in 70% of neoadjuvant treated patients. In summary, a therapy dedicated to destroying tumor blood vessels induced the development of lymphatic vessels, which may have contributed to the treatment failure. Cancer Res; 77(5); 1212-26. ©2017 AACR.

[Adaptation and validation of a brief screening questionnaire of depressive disorders in patients with cancer: Q2i study]. / Adaptation et validation d'un questionnaire à 2 items permettant le dépistage des troubles dépressifs chez les patients atteints de cancer : étude Q2i.

BACKGROUND: Depression is a sustainable state of deep sadness and abatement. It is frequently identified in patients with cancer and often undervalued by oncologists. The reduced PRIME-MD questionnaire is a questionnaire of 2 items validated in French. However, it has been neither translated nor validated in French. The objective of our study is to translate the PRIME-MD and validate it into French. METHOD: The PRIME-MD questionnaire was translated into French by using the recommendations of the EORTC and compared to the French gold standard questionnaire Mini-International Neuropsychiatric Interview (MINI). RESULTS: Two hundred and ninety-nine patients were included in our study. With a 98% filling rate, the Q2i questionnaire has been well accepted. The prevalence of depression in our population was measured at 7.4%. With a sensitivity of 89.47%, a specificity of 58.85%, found percentages are equal to those of the questionnaire in English. The negative predictive value was measured at 98.52%. CONCLUSION: This study demonstrates that the Q2i questionnaire is a quick and easy screening tool, requiring less than 2minutes to target patients likely to benefit from psychological support.

Salvage surgery for recurrent oropharyngeal cancer: post-operative oncologic and functional outcomes.

CONCLUSION: Post-operative outcomes of salvage surgery for recurrent oropharyngeal squamous-cell carcinoma (OPSCC) were acceptable. Pathologic overall, T- or N-stage and patient comorbidities were the main predictors of patient clinical outcomes. OBJECTIVES: To evaluate post-operative outcomes of salvage surgery in patients with recurrent OPSCC and to determine their predictive factors. MATERIALS AND METHODS: This study retrospectively reviewed the electronic medical records of all patients who underwent salvage surgery for recurrent OPSCC, between 2000-2013, in our institution. Overall survival (OS) and cause-specific survival (SS) were determined by Kaplan-Meier analysis. Predictive factors of post-operative outcomes were investigated by using univariate and multivariate analyses. RESULTS: A total of 34 patients were included in this study. Local and general post-operative complication rates were 26% and 27%, respectively. A high level of comorbidity (Kaplan Feinstein Index: KFI ≥ 2) was the only factor associated with a higher risk of local (p = 0.03) and general (p = 0.04) complications. OS and SS rates at 3 years were 48% and 61%, respectively. In multivariate analysis, pathologic overall stage ≥ III was a significant predictor of OS (p = 0.02) and pathologic T-stage ≥ 3 was a significant predictor of SS (p = 0.01). Mean pre-operative and post-operative DOSS (dysphagia outcome and severity scale) scores were 4.4 and 3.9, respectively.

[Multicenter validation study of a questionnaire assessing patient satisfaction with and acceptance of totally-implanted central venous access devices]. / Validation multicentrique d'un questionnaire évaluant l'acceptation et la satisfaction des patients porteurs de chambre à cathéter implantable : le questionnaire QASICC.

OBJECTIVE: Most cancer patients require a totally-implanted central venous access device (TIVAD) for their treatment. This was a prospective, multicenter, open study to: (i) develop and validate a French-language questionnaire dubbed QASICC (Questionnaire for Acceptance of and Satisfaction with Implanted Central Venous Catheter) assessing patient's satisfaction with and acceptance of their TIVAD; (ii) develop a mean score of patient's acceptance and satisfaction; (iii) look for correlation between QASICC score and TIVAD patient/tumor pathology/device characteristics. METHODS: From 2011 November to 2012 December, the first version of the QASICC questionnaire that included 27 questions assessing seven dimensions was re-tested among 998 cancer patients in eleven French cancer hospitals (eight cancer research institutes and three university/general hospitals). The goal was: (i) to reduce the questionnaire item and dimension number (pertinency, saturation effect, item correlation); (ii) to assess its psychometric properties, demonstrate its validity and independency compared to (EORTC) QLQC30; (iii) to correlate clinical and pathological patient's/tumor's/TIVAD's parameters with the QASICC questionnaire score (the higher the overall score, the greater the acceptance and satisfaction). The questionnaire was administered to the patient 30 days (±15 days) after TIVAD's implantation. RESULTS: Among 998 questionnaires given to cancer patients, 658 were analyzed and 464 were fully assessed as there was no missing data. Time to fill-in the questionnaire was five minutes in 90% patients. Final QASICC tool included twenty-two questions assessing four homogeneous dimensions (65%

Contemporary therapeutic management of locally advanced hypopharyngeal cancer: oncologic and functional outcomes - a report on 100 cases.

CONCLUSION: A significant proportion of patients with locally advanced hypopharyngeal cancer could not be managed by larynx-sparing therapy. T4 stage is one of the main predictive factors of oncologic and functional outcomes. OBJECTIVES: To analyze the therapeutic management of patients with locally advanced hypopharyngeal cancer in clinical practice and to report oncologic and functional outcomes. METHODS: This was a retrospective study of all patients treated for a locally advanced hypopharyngeal squamous cell carcinoma between 2001 and 2012 at our institution. RESULTS: A total of 100 patients were included in this study. Induction chemotherapy (CT) followed by radiotherapy (RT) ± CT, primary RT + CT, and primary total pharyngolaryngectomy (TPL) comprised the initial therapeutic management for 54, 24, and 20 patients, respectively. Two patients received only supportive care. Overall survival (OS) and cause-specific survival (SS) were 50% and 60% at 3 years, respectively. In the group of patients referred for induction CT, the 3-year OS and SS were 58% and 70%, respectively. In multivariate analysis, T stage (p = 0.05) and ASA score (p = 0.02) were significant predictive factors of OS. T4 tumor stage had a pejorative impact on swallowing function after therapy (p = 0.006). The rate of patients alive, disease-free, and with a functional larynx at 2 years was 23%.

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

CONCLUSIONS: Surgery for oral or oropharyngeal cancer with free-flap reconstruction is associated with moderate but persistent functional and quality of life (QoL) problems. Patient age, tumor stage, tumor site, and radiotherapy were the main predictors of functional outcome. OBJECTIVES: To evaluate long-term functional outcomes and QoL, and to determine their predictive factors in patients with oral or oropharyngeal cancer after oncologic surgery and free-flap reconstruction. METHODS: Patients who underwent surgery with free-flap reconstruction for oral or oropharyngeal cancer between 2000 and 2009 who were alive at least 1 year after therapy were included in this study. Patients completed the Voice Handicap Index (VHI-10) questionnaire and the European Organization for Research and Treatment of Cancer (EORTC) QoL questionnaires QLQ-C30 and H&N35. Swallowing was evaluated using the Dysphagia Outcome and Severity Scale (DOSS) and by flexible fiberoptic laryngoscopy. RESULTS: Sixty-four patients were included in the study. VHI-10 mean score was 11.2 ± 9 and its predictive factors were T stage (p = 0.005) and tumor involvement of the tongue base (p = 0.01). The mean DOSS score was 4 ± 0.8. Age (p = 0.008), gender (p = 0.04), and radiotherapy (p = 0.001) were the main predictive factors of the DOSS score.