Clinical validation of a prognostic tool in a population of outpatients treated for incurable cancer undergoing anticancer therapy: PRONOPALL study.

BACKGROUND: In 2008, a study of the characteristics of hospitalised patients led to the development of a prognostic tool that distinguished three populations with significantly different 2-month survival rates. The goal of our study aimed at validating prospectively this prognostic tool in outpatients treated for cancer in terminal stage, based on four factors: performance status (ECOG) (PS), number of metastatic sites, serum albumin and lactate dehydrogenase. PATIENTS AND METHODS: PRONOPALL is a multicentre study of current care. About 302 adult patients who met one or more of the following criteria: life expectancy under 6 months, performance status ≥ 2 and disease progression during the previous chemotherapy regimen were included across 16 institutions between October 2009 and October 2010. Afterwards, in order to validate the prognostic tool, the score was ciphered and correlated to patient survival. RESULTS: Totally 262 patients (87%) were evaluable (27 patients excluded and 13 unknown score). Median age was 66 years [37-88], and women accounted for 59%. ECOG PS 0-1 (46%), PS 2 (37%) and PS 3-4 (17%). The primary tumours were: breast (29%), colorectal (28%), lung (13%), pancreas (12%), ovary (11%) and other (8%). About 32% of patients presented one metastatic site, 35% had two and 31% had more than two. The median lactate dehydrogenase level was 398 IU/l [118-4314]; median serum albumin was 35 g/l [13-54]. According to the PRONOPALL prognostic tool, the 2-month survival rate was 92% and the median survival rate was 301 days [209-348] for the 130 patients in population C, 66% and 79 days [71-114] for the 111 patients in population B, and 24% and 35 days for [14-56] the 21 patients in population A. These three populations survival were statistically different (P <0.0001). CONCLUSION: PRONOPALL study confirms the three prognostic profiles defined by the combination of four factors. This PRONOPALL score is a useful decision-making tool in daily practice.

Use of liposomal doxorubicin-cyclophosphamide combination in breast cancer patients with brain metastases: a monocentric retrospective study.

Brain metastases (BM) can affect up to 45 % of a high-risk breast cancer (BC) population. Liposomal doxorubicin (LD)-based chemotherapy has demonstrated efficacy in the treatment of BC and LD crosses the blood-brain barrier. The aim of this retrospective study is to evaluate the efficacy of the LD-cyclophosphamide (CTX) combination in BM related to BC. Patients diagnosed with BM related to BC and treated with the LD-CTX combination were eligible. BM objective response rate (BM-ORR), BM disease control rate (BM-DCR), BM progression-free survival, overall survival (OS) and safety were analyzed. 29 patients were eligible. The median time from metastatic diagnosis to brain involvement was 12 months. BM was more frequently observed in HER2+ patients. On average, three courses of chemotherapy were administered without grade 3-4 limiting adverse events. After three cycles, BM-ORR and BM-DCR were 41.4 and 58.6 % respectively versus 50 and 62.5 % when no prior radiotherapy was administered. From BM diagnosis, OS was 23 months. A high BM-ORR is observed with the LD-CTX combination in patients with BM related to BC. This is an attractive therapeutic option for these patients, especially when no prior whole brain radiotherapy has been administered.

Efficacy and safety of early G-CSF administration in patients with head and neck cancer treated by docetaxel-cisplatin and 5-fluorouracil (DCF protocol): a retrospective study.

BACKGROUND: Induction chemotherapy with docetaxel-cisplatin and 5-fluorouracil (DCF) for locally advanced head and neck cancers (HNC) is associated with a high risk of severe neutropenia or febrile neutropenia (FN). We conducted a retrospective study to evaluate the efficacy and safety of administering granulocyte colony-stimulating factor (G-CSF) on day 3 (D3) during chemotherapy (early G-CSF stimulation) versus after the end of chemotherapy, as per current guidelines (i.e., after the end of 5-FU perfusion; D7), and its impact on patient outcomes. PATIENTS AND METHODS: Patients ≥19 years old, with advanced HNC who received DCF induction chemotherapy (D and P 75 mg per meter squared (mg/m(2)) on day 1 and 5-FU 750 mg/m(2)/day from D1 to D5), were included in the analysis. RESULTS: Data of 70 patients were analyzed from 01 January 2003 to 01 December 2010. Mean age was 56 years (range 45 to 77 years). Thirty-six patients (51.4 %) received pegfilgrastim on D7, and 28 (40 %) started G-CSF prophylaxis during chemotherapy; 12 (17.1 %) had daily filgrastim and 16 (22.9 %) pegfilgrastim on D3. Overall response rate (ORR) was 89.6 % (three early deaths due to infectious complications; 4.3 %). The 3-year overall survival (OS) rate was 72.8 %. FN rate was 14.3 % and chemotherapy delay was 12.9 %. In the D7 G-CSF arm, incidence of grade 3-4 neutropenia (p = 0.023), FN (p = 0.029), and cycle delays (p = 0.006) was statistically higher than the "early" G-CSF arm. A decrease of OS was observed at 2 years (from 85.1 to 63.5 %) of chemotherapy discontinuation or FN (p = 0.0348). DISCUSSION: Early administration of G-CSF is safe and seems to be more effective than D7. Future prospective trials are required to confirm our results.

Evaluation in usual practice of the bevacizumab-FOLFIRI combination for the first-line treatment of patients with unresectable metastatic colorectal cancer treated in 2006: focus on resected patients and oncogeriatrics: AVASTIN OUEST cohort of the Observatory of Cancer of the Brittany and Pays de la Loire Areas (Observatoire dédié au Cancer Bretagne / Pays de la Loire).

BACKGROUND: In 2006, bevacizumab, a targeted therapy agent was combined with FOLFIRI for the firstline treatment of patients with unresectable metastatic colorectal cancer. METHODS/RESULTS: A study on a homogenous series of 111 patients from the Brittany and Pays de la Loire areas who received bevacizumab-FOLFIRI as first-line treatment in 2006 showed the following results: 51 responses, 29 stabilisations, 21 progressions and 10 cases of toxicity prior to assessment. Median overall survival (OS) was 25.1 months and median progression-free survival was 10.2 months. Surgery secondary to treatment tripled median OS which reached 59.2 months in resected patients versus 18.8 months in unresected patients. Comparison of patients aged more or less than 70 years showed no differences in terms of benefits or risks. CONCLUSION: Bevacizumab-FOLFIRI could be administered as part of a routine care protocol to elderly patients previously evaluated by a geriatric assessment and validated by a multidisciplinary staff.

En 2006, bevacizumab-FOLFIRI représente la thérapie ciblée administrable dès la première ligne chez les patients porteurs d'un cancer colorectal métastatique non opérable. Une série homogène de 111 patients colligés en région Bretagne et Pays de la Loire ayant reçu du bevacizumab- FOLFIRI en première ligne en 2006 révèle les résultats suivants: 51 réponses, 29 stabilités, 21 progressions et 10 toxicités avant évaluation. La médiane de survie globale (OS) est de 25,1 mois et la médiane de survie sans progression (PFS) de 10,2 mois. Dans le cas d'une chirurgie secondaire, l'OS médian triple de 18,8 mois chez les patients non réséqués versus 59,2 mois ceux réséqués. En comparant les sujets âgés de plus et de moins de 70 ans, aucune différence n'a été mise en évidence en termes de bénéfice ou de risque. Bevacizumab-FOLFIRI pourrait être administré en pratique courante chez les personnes âgées sous couvert d'une évaluation gériatrique et d'une approche multidisciplinaire.

Rehabilitation following total laryngectomy: Oncologic, functional, socio-occupational and psychological aspects.

GOAL: To review rehabilitation following total laryngectomy by an analysis of epidemiological, oncologic and functional data. MATERIALS AND METHODS: This retrospective observational study focused on patients having undergone total laryngectomy or pharyngolaryngectomy between January 1, 2005 and December 31, 2016. Oncologic data notably comprised survival and relapse and predictive factors. The impact of the procedure on quality of life and the voice was analyzed by self-administered questionnaires (EORTC QLQ-C30 and H&N35, VHI 30). A satisfaction questionnaire was also sent to patients. RESULTS: One hundred and thirty three patients were included. Overall specific 5-year survival was 65%. The relapse rate was 32%. Factors influencing survival were WHO performance status ≥2 (P<0.05), tumor location (P=0.07), metastatic lymphadenopathy (P=0.017) and positive resection margins (P=0.01). Quality of life was moderately degraded (global EORTC QLQ-C30 status: 61.4±23.9). Type of rehabilitation (P=0.03), tube feeding (P=0.03) and relapse (P<0.01) influenced quality of life. There were no differences in voice quality according to rehabilitation method, and no predictive factors for failure of voice rehabilitation. More than 90% of patients were satisfied with their hospital stay; 43%, however, were not satisfied with community caregiver training for laryngectomy patients. CONCLUSION: Rehabilitation of laryngectomized patients is a current therapeutic challenge. A therapeutic education tool was designed to better meet patient expectations.

The influence of fluorouracil outcome parameters on tolerance and efficacy in patients with advanced colorectal cancer.

The purpose of this study was to determine simple genetic factors helpful to tailor 5-FU administration and determine strategy in first-line chemotherapy of advanced colorectal cancer. In 76 patients initially treated by 5-FU, thymidylate synthase, dihydropyrimidine dehydrogenase and methylene tetrahydrofolate reductase germinal polymorphisms, dihydrouracil/uracil plasma ratio and 5-FU plasma clearance were investigated and correlated for tolerance (10.5% grade 3 and 4 toxicity) and efficacy (32.9% objective response rate and 20 months median overall survival time). Toxicity was linked to performance status >2 (P=0.004), low UH2/U ratio, 2846 A>T, IVS 14+1G>A for DPD (P=0.031), and homozygoty C/C for MTHFR 1298 A>C (P=0.0018). The overall survival of the patients with a 3R/3R TS genotype associated with C/C for 677 C>T or A/A for 1298 A>C was statistically shorter (log-rank test P=0.0065). Genetic factors permit the tailoring of 5-FU treatment. They should occupy center stage in future clinical trials for specifically designing treatment for patients with a given biologic feature.

[Multifocal adult rhabdomyoma and positron emission tomography]. / Rhabdomyome multifocal et tomographie par émission de positons.

OBJECTIVES: We report the first case of a multifocal adult extracardiac rhabdomyoma discovered on positron emission tomography and provide a brief review of the literature on this entity. MATERIAL AND METHODS: Multifocal rhabdomyoma was discovered in a 65-year-old asymptomatic man on positron emission tomography (PET). Surgery was undertaken, allowing histological diagnosis. RESULTS: Adult rhabdomyoma is a rare mesenchymal tumor which generally grows slowly and is mainly localized in the head and neck area. Multifocal lesions are rare. PET (undertaken to explore a pulmonary nodule) found three fixations in the head and neck area, confirmed by tomodensitometry and MRI, without providing the diagnosis. This situation led to a surgical exploration. CONCLUSION: This observation revealed that rhabdomyoma can fix the PET scan. Tomodensitometry and MRI can also specify the tumor extension to define the treatment methods. Surgery must be preserving and is indicated only in the event of symptomatic tumor.

Osteoporosis treatment and 10 years' oestrogen receptor+ breast cancer outcome in postmenopausal women treated with aromatase inhibitors.

BACKGROUND: Risk factors for breast cancer relapse are well-known, such as large tumour size or lymph node involvement. The aim of our study was to analyse the influence of bone mineral density, fractures and bisphosphonate or vitamin D prescription on 10 years' breast cancer outcome. PATIENTS AND METHODS: This is a longitudinal and prospective cohort of 450 postmenopausal women with local oestrogen receptor (ER)+ breast cancer. For every patient, we analysed tumour characteristics, bone status at the beginning of aromatase inhibitor treatment and 10 years' cancer outcome with Cox model. RESULTS: Mean follow-up was 10.3 ± 3.0 years. Seventy nine women died, and 75 had a relapse; 30.7% had a history of fracture, 16.9% had a T-score ≤ -2.5 and 11.3% had vitamin D deficiency. Bisphosphonates were prescribed to 35.3% women for osteoporosis for a mean duration of 5 ± 1.7 years. Tumour size (hazard ratio [HR] = 1.32, P ≤ 0.01) and the number of lymph nodes involved (HR = 1.07, P = 0.03) were significantly associated with relapse. Bisphosphonate treatment was significantly associated with a decreased risk of relapse (HR = 0.51, P = 0.03). Age at cancer diagnosis (HR = 1.07, P ≤ 0.01) and vitamin D deficiency (HR = 1.85, P = 0.04) were significantly associated with an increased risk of death, whereas bisphosphonate treatment was associated with a decreased risk of death (HR = 0.46, P = 0.01). CONCLUSION: Osteoporosis treatment, including vitamin D and bisphosphonates, is associated with a 50% reduction of relapse and death in women treated with aromatase inhibitors for ER+ breast cancer.

[Pharmacogenetics of anti-cancer drugs]. / Pharmacogénétique des anticancéreux.

Toxic side-effects of cytotoxic drugs is a stumbling-block of chemotherapy due to the fact that their therapeutic index is narrow. New approaches are necessary to individualize the treatments. Pharmacogenetic analysis is facilitated by easy access to the patient genome via simple blood samples, by the large number of known genes of interest coding for drugs targets or metabolism enzymes and by the fact that their polymorphism (SNP) is often known. Presently more focused on the prevention of toxic side-effects, pharmacogenetics already provides a good deal of confirmed data for clinical applications, such as the detection of dihydropyrimidine dehydrogenase deficiency by sequencing, or UGT1A1 7/7 genotype detection in Gilbert's syndrome for the prevention of 5-FU and irinotecan-induced severe toxicities. It must be emphasized that a SNP which is deleterious for enzyme activity is rarely a contraindication for the drug, provided that some precautions are taken and appropriate therapeutic advice is given by experts.

Curative cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis and synchronous resectable liver metastases arising from colorectal cancer.

OBJECTIVES: This study describes the outcomes of patients with colorectal peritoneal carcinomatosis (PC) with or without liver metastases (LMs) after curative surgery combined with hyperthermic intraperitoneal chemotherapy, in order to assess prognostic factors. BACKGROUND: Cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) increases overall survival (OS) in patients with PC. The optimal treatment both for PC and for LMs within one surgical operation remains controversial. METHODS: Patients with PC who underwent CRS followed by HIPEC were evaluated from a prospective database. Overall survival and disease free survival (DFS) rates in patients with PC and with or without LMs were compared. Univariate and multivariate analyses were performed to evaluate predictive variables for survival. RESULTS: From 1999 to 2011, 22 patients with PC and synchronous LMs (PCLM group), were compared to 36 patients with PC alone (PC group). No significant difference was found between the two groups. The median OS were 36 months [range, 20-113] for the PCLM group and 25 months [14-82] for the PC group (p > 0.05) with 5-year OS rates of 38% and 40% respectively (p > 0.05). The median DFS were 9 months [9-20] and 11.8 months [6.5-23] respectively (p = 0.04). The grade III-IV morbidity and cytoreduction score (CCS) >0 (p < 0.05) were identified as independent factors for poor OS. Resections of LMs and CCS >0 impair significantly DFS. CONCLUSIONS: Synchronous complete CRS of PC and LMs from a colorectal origin plus HIPEC is a feasible therapeutic option. The improvement in OS is similar to that provided for patients with PC alone.

[Prognostic value of the metabolically active tumour volume]. / Valeur pronostique du volume tumoral métabolique sur la TEP au ((18)F)-fluorodésoxyglucose préthérapeutique pour le cancer de l'œsophage localisé.

PURPOSE: The purpose of this study was to assess the prognostic value of different parameters on pretreatment fluorodeoxyglucose [((18)F)-FDG] positron emission tomography-computed tomography (PET-CT) in patients with localized oesophageal cancer. PATIENTS AND METHOD: We retrospectively reviewed 83 cases of localised oesophageal cancer treated in our institution. Patients were treated with curative intent and have received chemoradiotherapy alone or followed by surgery. Different prognostic parameters were correlated to survival: cancer-related factors, patient-related factors and parameters derived from PET-CT (maximum standardized uptake value [SUV max], metabolically active tumor volume either measured with an automatic segmentation software ["fuzzy locally adaptive bayesian": MATVFLAB] or with an adaptive threshold method [MATVseuil] and total lesion glycolysis [TLGFLAB and TLGseuil]). RESULTS: The median follow-up was 21.8 months (range: 0.16-104). The median overall survival was 22 months (95% confidence interval [95%CI]: 15.2-28.9). There were 67 deaths: 49 associated with cancer and 18 from intercurrent causes. None of the tested factors was significant on overall survival. In univariate analysis, the following three factors affected the specific survival: MATVFLAB (P=0.025), TLGFLAB (P=0.04) and TLGseuil (P=0.04). In multivariate analysis, only MATVFLAB had a significant impact on specific survival (P=0.049): MATVFLAB<18 cm(3): 31.2 months (95%CI: 21.7-not reached) and MATVFLAB>18 cm(3): 20 months (95%CI: 11.1-228.9). CONCLUSION: The metabolically active tumour volume measured with the automatic segmentation software FLAB on baseline PET-CT was a significant prognostic factor, which should be tested on a larger cohort.

[Cytolytic hepatitis and esomeprazole during chemotherapy]. / Hépatite cytolytique due à l'ésoméprazole au cours d'une chimiothérapie anticancéreuse.

INTRODUCTION: Esomeprazole, the pure S isomer form of omeprazole, is indicated for the treatment of peptic esophagitis. We report here a major episode of cytolytic hepatitis following a single administration. CASE: A 41-year-old woman with infiltrating ductal carcinoma of the breast was undergoing chemotherapy with paclitaxel and trastuzumab. On the fourth day of the second course, she took 1 tablet of esomeprazole 20 mg for epigastric pain. Liver pain and asthenia followed, and liver function tests showed substantial cytolysis. These tests returned to normal levels despite continuation of the chemotherapy. DISCUSSION: This cytolytic hepatitis is very probably imputable to esomeprazole, but a synergistic hepatic toxicity of the chemotherapy with esomeprazole cannot be ruled out.

[Are extensive fields useful for radiotherapy of esophageal cancer?]. / Des marges extensives sont-elles nécessaires pour la radiothérapie du cancer de l'œsophage ?

PURPOSE: Study of the pattern of relapse for locally advanced oesophageal cancer and analysis of the local recurrences according to irradiated volume. PATIENTS AND METHODS: We performed a monocentric retrospective study of patients treated in the integrated centre of oncology (Angers, France). Two treatment strategies were used: concurrent chemoradiation alone or followed by surgery. Recurrences were classified as: locoregional, either isolated or associated with distant metastasis, and metastatic only. Locoregional relapses were subclassified as in-field, out-field, or mixed. RESULTS: Between March 2004 and October 2011, 168 patients were treated: 130 by chemoradiation, and 38 by chemoradiation followed by surgery. The median supero-inferior margins added to the gross tumour volume in order to create the planning tumour volume was 5cm (range: 0.5-21). Sixty-two percent of patients (n=104) relapsed: 82 locoregional relapses (49%), including 45 isolated relapses (27%) and 37 associated with distant metastasis relapses (22%), and 22 metastatic relapses (13%). From the 82 locoregional relapses, only four isolated relapses were exclusively out-field. CONCLUSION: With 5cm supero-inferior margins added to gross tumour volume, less than 3% of patients had an isolated out-field recurrence. However, half of the patients suffered in-field local recurrence and one third had metastases. These findings advocate for a limited prophylactic nodal irradiation. Trials are ongoing to assess dose escalation or surgery in order to increase local control.

[Recurrence sites following definitive intensity-modulated conformational radiotherapy of squamous-cell carcinomas of the upper aerodigestive tract]. / Sites de récidive après radiothérapie conformationnelle avec modulation d'intensité des carcinomes épidermoïdes des voies aérodigestives supérieures.

PURPOSE: The implementation of intensity-modulated radiotherapy (IMRT) in a centre requires regular critical review of medical practices and feedback to optimize the subsequent management of patients. PATIENTS AND METHODS: We reviewed and determined through a retrospective single-centre study recurrence sites of 167 consecutive patients treated for head and neck squamous cell carcinoma excluding skin or sinuses. Patients had mostly stage III or IV locally advanced cancer (n=123). RESULTS: Locoregional control rates at 1 and 2 years were respectively 87.9% (95% confidence interval [95%CI]: 81.6%-92.1%) and 77.6% (95%CI: 70.1%-83.5). Among 55 relapses, 20 patients (36.4%) had treatment failures. Patients treated with 70 Gy relapsed mainly in high risk volume (78%). Those treated with 66 Gy recurred regionally outside the irradiated volume (n=4) or in the irradiated high risk volume (n=3) or had isolated metastatic failure (n=3). Those irradiated with 50 Gy had regional relapse outside the irradiated volume (n=2) or isolated metastatic relapse (n=2). We noticed respectively 5.4%, 10.2% and 4.2% isolated metastatic, local, cervical lymph node relapse. CONCLUSION: Our results are consistent with data from the literature. Corrective actions were performed to enhance our practices.

[Esophageal cancer: outcome according to therapeutic strategy]. / Évolution des cancers de l'œsophage : impact de la stratégie thérapeutique.

PURPOSE: To assess the outcome of esophageal cancer according to therapeutic strategy. PATIENTS AND METHODS: One-hundred and twenty patients with esophageal cancer treated by an association of radiotherapy and chemotherapy and possibly surgery, between 2004 and 2010, were retrospectively studied. The first site of relapse was classified as follows: local (tumour), locoregional (tumour and/or nodal: celiac, mediastinal, sus-clavicular) or metastatic. RESULTS: With a 15.7-months (1.4-62) median follow-up, there were 89 deaths and 79 recurrences. Three types of treatments were performed: 50Gy exclusive chemoradiotherapy (47 patients) or 50 to 65Gy exclusive chemoradiotherapy (44 patients) or chemoradiotherapy followed by surgery (27 patients). The local first relapse was as much frequent as distant relapse (50 patients). With a-5cm margin up and down to the tumour, there was only one nodal relapse. Two-year survival was 39.5% (95% confidence interval [IC]: 30.5-40.8) and relapse-free survival was 26.5% (CI: 18.6-35). Multivariate analysis revealed that treatment type and disease stage had a significant impact on survival, relapse-free survival and locoregional control. Compared to exclusive chemoradiotherapy, surgery improved locoregional control (40.2 versus 8.7 months, P=0.0004) but in a younger population. Despite postoperative mortality, the gain was maintained for distance relapse-free survival (40.2 versus 10 months, P=0.0147) and overall survival (29.3 versus 14.2 months, P=0.0088). Compared to 50Gy chemoradiotherapy, local control was improved if high dose chemoradiotherapy was performed (13.8 versus 7.5 months, P=0.05) but not overall survival (14.0 versus 15.4 months, P=0.24). CONCLUSION: More than one-third relapse is local. Locoregional control is better with high dose chemoradiotherapy. In this study, surgery performed in selected patients only, improved locoregional control, relapse-free disease and overall survival.