Prolonged efficacy of pembrolizumab in a patient presenting a multi-treated metastatic hepatocholangiocarcinoma.

INTRODUCTION: Hepatocholangiocarcinoma (HCC-ICC) is a rare tumor presenting the histologic characteristics of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). As there is no consensus on it management, the therapeutic strategy rests on the specific treatments for HCC or ICC. Programmed cell death 1 (PD-1) inhibitors showed encouraging results in the second line treatment of HCC after sorafenib but it efficacy in HCC-ICC has never been reported. METHODS AND RESULTS: We present the case of a 72-year-old male patient treated for metastatic HCC-ICC due to a viral hepatitis C cirrhosis in progression after two lines of treatment. Tumor was characterized by a PDL-1 status of 85%. Patient received pembrolizumab at doses of 200 mg every 21 days by intravenous infusion. After one injection he was presented an immediate clinical benefit, a partial response was observed after two months of treatment and a complete response two months later. This response was maintained over time along with toxicity-free tumor control after 18 months treatment. CONCLUSION: To our knowledge, we reported for the first time the efficacy of a PD1 inhibitor treatment in a patient presenting metastatic HCC-ICC due to viral cirrhosis and overexpressing PDL-1 after failure of two lines of treatment.

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.

Long term efficacy and toxicity after stereotactic ablative reirradiation in locally relapsed stage III non-small cell lung cancer.

BACKGROUND: In stage III non-small cell lung cancer (NSCLC) treated with concomitant chemoradiotherapy, there is a high rate of relapse. Some of these relapses are only local and can be treated by stereotactic ablative radiation therapy (SABR). Previous studies reporting outcome after SABR reirradiation of the thorax consisted of a heterogeneous population of various lung cancer stages or even different types of cancer. The purpose of study is to evaluate toxicity and outcome of this strategy in locally relapsed stage III NSCLC only. METHODS: From February 2007 to November 2015, 46 Stage III NSCLC patients treated with SABR, for lung recurrence following conventionally fractionated radiation therapy (CFRT), were retrospectively analyzed. RESULTS: Median follow-up was 47.3 months (1-76.9). The 2 and 4-year progression-free survival (PFS), and overall survival (OS) were of 25.5%/8.6 and 48.9%/30.8%, respectively. Highest presenting toxicity in patients (grade 1 through 5) was: 13 (28.3%), 7 (15.2%), 1 (2.2%), 0 and 2 (4.4%), with deaths due to hemoptysis (n = 1) and alveolitis (n = 1). Although the Biological Effective Dose (at Planning Tumor Volume isocenter) was lower for central tumors treated for an in-field relapse (n = 21, 116 Gy versus 168 Gy, p = 0.005), they had no significant difference in OS than the remaining cohort, but with a higher rate of grade 2-5 toxicities (OR = 0.22, [0.06-0.8], p = 0.02). CONCLUSION: Reirradiation with SABR for local relapse in patients previously treated for stage III NSCLC, is feasible and associated with good outcome. This is also true for central tumors treated for an in-field relapse, but should be radiated with caution to mitigate toxicity.

Evolution and predictive factors of quality of life in patients undergoing oncologic surgery for head and neck cancer: A prospective multicentric study.

OBJECTIVES: The purposes of this study were to assess the evolution of quality of life (QoL) in patients with head and neck squamous cell carcinoma (HNSCC) undergoing oncologic surgery and to determine the predictive factors of post-therapeutic QoL. METHODS: All HNSCC patients who underwent primary surgery, between 2012 and 2014, were enrolled in this prospective multicentric study. Patients completed the EORTC QLQ-C30 and QLQ-H&N35 questionnaires before surgery and at 6 months after treatment. Predictive factors of post-therapeutic QoL scores were determined. RESULTS: A total of 200 patients were included in this study. There was no significant deterioration of global QoL and no significant increase in general symptoms between the pre- and post-therapeutic periods, but a significant deterioration in role and social functioning, and an increase of most head and neck symptoms. Tumor stage, tumor site and treatment modalities (type of surgery, adjuvant therapy) were the main predictors of QoL scores. We found a negative correlation between satisfaction with the information received and global QoL score or several functioning scales. CONCLUSION: HNSCC surgical treatment affects patients QoL mainly by increasing head and neck symptoms, which results in social and role functioning deterioration. These results are of great interest to improve multidisciplinary care of HNSCC patients.

Stereotactic ablative radiotherapy after concomitant chemoradiotherapy in non-small cell lung cancer: A TITE-CRM phase 1 trial.

BACKGROUND AND PURPOSE: Platinum based chemoradiotherapy is the standard of care for inoperable non-small cell lung cancer (NSCLC). With evidence that NSCLC can have a dose dependent response with stereotactic ablative radiotherapy (SABR), we hypothesize that a SABR boost on residual tumor treated with chemoradiotherapy could increase treatment efficacy. The purpose of this study was to determine feasibility of such an approach. MATERIAL AND METHODS: A prospective phase I trial was performed including 26 patients. Time-to-event continual reassessment method (TITE-CRM) was used for dose escalation which ranged from 3 × 7 to 3 × 12 Gy for the stereotactic boost, after 46 Gy (2 Gy per day) of chemoradiotherapy. RESULTS: Median follow-up was of 37.1 months (1.7-60.7), and 3, 4, 3, 3, 9 and 4 patients were included at the dose levels 1, 2, 3, 4, 5 and 6, respectively. During chemoradiotherapy, 9 patients experienced grade 3 toxicity. After stereotactic radiotherapy, 1 patient experienced an esophageal fistula (with local relapse) at the 3 × 11 Gy level, and 1 patient died from hemoptysis at the 3 × 12 Gy level. The 2-year rate of local control, locoregional free survival, metastasis-free survival, and overall survival was 70.3%, 55.5%, 44.5% and 50.8%, respectively. CONCLUSION: In the treatment of NSCLC with chemoradiotherapy followed by a stereotactic boost, the safe recommended dose in our protocol was a boost dose of 3 × 11 Gy.

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.

Radiosensitivity of Colon and Rectal Lung Oligometastasis Treated With Stereotactic Ablative Radiotherapy.

INTRODUCTION: Patients with metastatic colorectal cancer (CRC) may present with oligometastatic lung lesions for which stereotactic ablative radiotherapy (SABR) can be utilized. This study aims to report efficacy and prognostic factors associated with colorectal lung metastases treated with SABR. MATERIAL AND METHODS: This is a retrospective study including patients who presented with lung oligometastasis from CRC treated with SABR from September 2007 to November 2014. RESULTS: We identified 53 oligometastatic patients with 87 lung lesions. The median prescription dose was 60 Gy in 3 fractions (median biological effective dose of 180 Gy). The median follow up was 33 months. The 1- and 2-year local control, metastasis-free survival, and overall survival were 79.8% and 78.2%, 29.2% and 16.2%, and 83.8% and 69.3%, respectively. On multivariate analysis, rectal primary site (P = .001) and > 2 metastases (P = .02) were significantly associated with a lower local control rate. Rectal lesions were associated with higher radiation dose (169.3 Gy vs. 153.3 Gy; P = .01) and higher rate of KRAS mutations (73.3% vs. 40.4%; P = .02). KRAS mutation did not predict for local control, but predicted for a 1-year metastasis-free survival detriment (0% vs. 37.5%; P = .04), when compared with KRAS wild-type. On multivariate analysis, there is an overall survival detriment associated with gross tumor volume ≥ 3266 mm3 (P = .03) and > 2 metastases (P = .04). CONCLUSION: In CRC, oligometastatic lung lesions treated with SABR had a worse outcome in patients presenting with a rectal primary, > 2 metastases, or treated with a larger gross tumor volume. More aggressive treatment may be considered in this subset of patients to improve outcome.

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.

Evaluation of the information given to patients undergoing head and neck cancer surgery using the EORTC QLQ-INFO25 questionnaire: A prospective multicentric study.

AIM: Providing head and neck cancer patients with adequate information is essential to their confidence and satisfaction regarding medical care. The aims of this study were to evaluate patient perceptions of the information received, the predictive factors of such perceptions and their potential correlation with patient quality of life (QoL). METHODS: We conducted a prospective multicentric study using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-INFO25 and QLQ-C30 questionnaires before and after surgery. RESULTS: This study enrolled 200 patients, 149 men and 51 women, mean age 63.5 ± 10.3 years. Before and after treatment, global QLQ-INFO25 scores were 39.3 and 42.5, respectively, whereas satisfaction with the information received scores were 69.9 and 58.1, respectively. Regarding EORTC QLQ-INFO25 scores, between the pre- and post-treatment periods, we observed a significant increase in three scales/items (information about other services, information about different places of care and information about things you can do to help yourself) and a significant decrease in two scales/items (satisfaction with the information received and overall the information has been helpful). Before and after treatment, global QoL scores were 62.7 and 61.0, respectively. Overall, we found low correlations between QLQ-INFO25 and QLQ-C30 scores. Patient age and education level, centre of care, tumour site and treatment characteristics had a significant impact on QLQ-INFO25 scores. CONCLUSION: Perceived information was satisfactory in the perioperative period for head and neck cancer patients. Several demographic and clinical factors were identified as significant predictors of QLQ-INFO25 scores.

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.

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.

[Advances in radiation oncology for metastatic bone disease]. / Métastases osseuses : les nouvelles techniques d'irradiation et traitements combinés ablatifs décalent-ils les standards ?

INTRODUCTION: Irradiation of bone metastases primarily aims at alleviating pain, preventing fracture in the short term. The higher doses and more conformal dose distribution achievable while saving healthy tissue with new irradiation techniques have induced a paradigm shift in the management of bone metastases in a growing number of clinical situations. MATERIALS AND METHODS: A search of the English and French literature was conducted using the keywords: bone metastases, radiotherapy, interventional radiology, vertebroplasty, radiofrequency, chemoembolization. RESULTS-DISCUSSION: Stereotactic irradiation yields pain relief rates greater than 90% in Phase I/II and retrospective studies. IMRT (static, rotational, helical) and stereotactic irradiation yield local control rates of 75-90% at 2 years. Some situations previously evaluated as palliative are currently treated more aggressively with optimized radiation sometimes combined modality interventional radiology. CONCLUSION: A recommendation can only be made for stereotactic irradiation in vertebral oligometastases or reirradiation. In the absence of a sufficient level of evidence, the increasing use of conformal irradiation techniques can only reflect the daily practice and the patient benefit while integrating economic logic care. The impact of these aggressive approaches on survival remains to be formally demonstrated by interventional prospective studies or observatories including quality of life items and minimal 2-year follow-up.

[Radiotherapy of bone metastases]. / Prise en charge par radiothérapie des métastases osseuses et de leurs complications : les standards.

Sixty percent of cancer patients have or develop bone metastases during the development of their cancer. Bone metastases are the most common cause of cancer-related pain. External radiation therapy is the standard treatment of uncomplicated bone metastases, for the treatment of pain, the prevention of fracture, and for tumor control. Fractionation schedules (one session of 8 Gy or several sessions, typically 30 Gy in 10 fractions) vary in terms of efficacy with however more retreatments after a single session. The treatment of spinal cord compression is classically based on radiotherapy associated or not with surgery with indications assessed in emergency by a multidisciplinary team. The use of prognostic scores and prospective studies including patients corresponding to the daily practice and the work of groups like the GEMO aim to harmonize and optimize the management of bone metastases.

Features of cancer management in obese patients.

There is worldwide increased in obesity prevalence and statistical almost half of United-States, including children, could be obese by 2050. Obesity in cancer patients is a major issue in oncology because weight gain and obesity account for approximately 20% of all cancer cases. Indeed, increased obesity is linked with higher risk of various types of cancer and a poorer survival. Although biological mechanisms underlying how obesity causes an increased risk of cancer are suggested, overweight as a putative direct cause of death is still debated. Numerous confounding factors may impact on survival, including comorbidities and imaging limitations. Moreover, difficulties to achieve the standard oncologic care with surgery, chemotherapy and/or radiation may also be concerned. Herein, we examined the specific features and potential adaptation of the cancer management in overweighed patients. Then, we reviewed how implicated molecular pathways may provide new strategies to decrease cancer risk and predict toxicities in an increasingly obese population.