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1.
World J Urol ; 41(10): 2715-2722, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37555987

ABSTRACT

PURPOSE: This study aimed at describing the feasibility and oncological outcomes of standard cisplatin-based neoadjuvant chemotherapy (C-NAC) for muscle-invasive bladder cancer (MIBC) in patients aged ≥ 75 and assess the impact of baseline geriatric parameters. METHODS: This retrospective study included patients with stage cT2-4NanyM0 MIBC aged 75 and older treated with ≥ 1 cycle of C-NAC from 2011 to 2021 at a high-volume academic center. Primary outcome was overall survival (OS). Secondary outcomes were chemotherapy feasibility (administration of ≥ 4 cycles), safety, and pathological downstaging. RESULTS: Fifty-six patients were included. Median age was 79 (range 75-90). C-NAC regimen was ddMVAC in 41 patients and GC in 15. Seventy-three percent of patients received ≥ 4 cycles of C-NAC. Grade ≥ 3 toxicity was observed in 55% of patients. The febrile neutropenia rate was 7%. Thirty patients underwent cystectomy, and 13 underwent chemoradiotherapy. Three-year OS was 63%. Geriatric parameters polypharmacy, undernutrition, and age-adjusted Charlson comorbidity index ≥ 8 predicted worse OS. CONCLUSION: Standard-of-care C-NAC and local treatments are feasible in selected elderly MIBC patients, with efficacy and safety findings similar to that observed in pivotal trials with younger patients. The prognostic impact of geriatric parameters underlines the need for specialized evaluation before treatment initiation.


Subject(s)
Urinary Bladder Neoplasms , Aged , Humans , Retrospective Studies , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/surgery , Cisplatin/therapeutic use , Prognosis , Neoadjuvant Therapy , Chemotherapy, Adjuvant , Cystectomy , Muscles , Neoplasm Invasiveness
2.
Pediatr Blood Cancer ; 70(11): e30615, 2023 11.
Article in English | MEDLINE | ID: mdl-37574821

ABSTRACT

PURPOSE: We report the results of the French multicentric phase II study MIITOP (NCT00960739), which evaluated tandem infusions of 131 I-metaiodobenzylguanidine (mIBG) and topotecan in children with relapsed/refractory metastatic neuroblastoma (NBL). METHODS: Patients received 131 I-mIBG on day 1, with intravenous topotecan daily on days 1-5. A second activity of 131 I-mIBG was given on day 21 to deliver a whole-body radiation dose of 4 Gy, combined with a second course of topotecan on days 21-25. Peripheral blood stem cells were infused on day 31. RESULTS: Thirty patients were enrolled from November 2008 to June 2015. Median age at diagnosis was 5.5 years (2-20). Twenty-one had very high-risk NBL (VHR-NBL), that is, stage 4 NBL at diagnosis or at relapse, with insufficient response (i.e., less than a partial response of metastases and more than three mIBG spots) after induction chemotherapy; nine had progressive metastatic relapse. Median Curie score at inclusion was 6 (1-26). Median number of prior lines of treatment was 3 (1-7). Objective response rate was 13% (95% confidence interval [CI]: 4-31) for the whole population, 19% for VHR-NBL, and 0% for progressive relapses. Immediate tolerance was good, with nonhematologic toxicity limited to grade-2 nausea/vomiting in eight patients. Two-year event-free survival was 17% (95% CI: 6-32). Among the 16 patients with VHR-NBL who had not received prior myeloablative busulfan-melphalan consolidation, 13 had at least stable disease after MIITOP; 11 subsequently received busulfan-melphalan; four of them were alive (median follow-up: 7 years). CONCLUSION: MIITOP showed acceptable tolerability in this heavily pretreated population and encouraging survival rates in VHR-NBL when followed by busulfan-melphalan.


Subject(s)
Neuroblastoma , Topotecan , Adolescent , Child , Child, Preschool , Humans , Young Adult , 3-Iodobenzylguanidine/adverse effects , Busulfan/therapeutic use , Chronic Disease , Melphalan , Neoplasm Recurrence, Local/drug therapy , Neuroblastoma/drug therapy , Neuroblastoma/radiotherapy
3.
World J Urol ; 41(11): 3249-3255, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37410102

ABSTRACT

PURPOSE: to assess the respective outcomes of patients with localized muscle-invasive bladder cancer (MIBC) treated by either radical cystectomy (RC) or trimodal treatment (TMT) depending on pathological response to previous neoadjuvant chemotherapy (NAC) assessed on cystectomy specimen or post-NAC transurethral resection (TURB) specimen, respectively. PATIENT AND METHODS: We retrospectively included all consecutive patients treated in one academic center with cisplatin-based NAC followed by RC or TMT for cT2-3N0M0 MIBC between 2014 and 2021. Primary endpoint was metastasis-free survival (MFS) in both treatment groups and according to pathological response to NAC. Local recurrence-free survival and conservative management failure (metastasis-free bladder-intact survival) for patients treated with TMT were assessed. RESULTS: 104 patients were included, 26 treated with TMT and 78 with RC. The rate of complete pathological response was 47.4% in patients treated with RC (ypT0) and 66.7% in patients treated with TMT (ycT0). Median follow-up was 34.9 months. Four-year MFS was 72% in both treatment groups. Four-year MFS was 85% in both ypT0 RC patients and ycT0 TMT patients. ycT0 stage was associated with low rates of intravesical recurrence and conservative management failure. CONCLUSION: Patients with post-NAC ycT0 stage treated with TMT have favorable oncological outcomes similar to those of ypT0 patients treated with RC. Assessment of complete histological response with TURB after NAC may help in selecting the best candidates for bladder preservation with TMT.


Subject(s)
Urinary Bladder Neoplasms , Urinary Bladder , Humans , Urinary Bladder/pathology , Cystectomy , Neoadjuvant Therapy , Retrospective Studies , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/surgery , Muscles , Neoplasm Invasiveness/pathology
4.
Immunotherapy ; 15(10): 729-735, 2023 07.
Article in English | MEDLINE | ID: mdl-37139988

ABSTRACT

Background: The optimal duration of treatment for metastatic patients who achieve a complete response with immune checkpoint inhibitors is unknown. Methods: The outcome for six metastatic bladder cancer patients who received short course of pembrolizumab is reported. Results: A median number of seven cycles of pembrolizumab was given. After a median follow-up of 38 months, progressive disease was confirmed in three patients. All patients relapsed in lymph nodes and underwent pembrolizumab rechallenge: one achieved a complete response, another a partial response. Conclusion: Our case series paves the way for discontinuation of pembrolizumab in patients who achieve a complete response since three out of six patients remain free of disease after 3-year follow-up. Prospective studies are required to confirm our results.


The rise of immunotherapy in oncology has provided significant gains in survival of metastatic patients. However, questions persist about the optimal use of immune checkpoint inhibitors. For now, treatment is supposed to be delivered until progression of disease. We report a case series of six patients who received a short course of treatment after achieving a complete response. Three of them remained free of recurrence after a median follow-up of 3 years. Our results suggest that a stop-and-go strategy might be appropriate for some patients, thereby sparing the potential toxicities associated with prolonged exposure.


Subject(s)
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/drug therapy , Carcinoma, Transitional Cell/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Immune Checkpoint Inhibitors/therapeutic use
5.
Case Rep Oncol ; 15(2): 745-749, 2022.
Article in English | MEDLINE | ID: mdl-36157695

ABSTRACT

Heart metastases from urothelial carcinoma of the bladder have rarely been reported in the literature. We present a case complicated by symptomatic disseminated intravascular coagulation in a 67-year-old woman. A rapid and sustained recovery from hemostatic troubles was obtained following fibrinogen supplementation combined with second-line paclitaxel chemotherapy.

6.
J Thromb Thrombolysis ; 53(2): 417-424, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34296382

ABSTRACT

INTRODUCTION: Treatment of Venous thromboembolism (VTE) in cancer patients is challenging due to higher risk of VTE recurrence or bleeding under anticoagulants. We assessed the effectiveness of a dedicated "Allo-Thrombosis Cancer" multidisciplinary care program (AlloTC-MCP) that incorporated individualized care, regular follow-ups, telephone counselling, and a patient education program. METHODS AND MATERIALS: From September 2017 to October 2019, 100 consecutive cancer patients with new VTE onset were enrolled in this observational single-center prospective pilot study and received standard (control group, n = first 50 patients enrolled) or AlloTC-MCP care (n = next 50 patients enrolled) over a 6-month VTE treatment follow-up period. Primary end-point was the percentage of adherence to the International Clinical Practice Guidelines (ITAC-CPGs) at 6 (M6) month follow-up. RESULTS: Among the 100 patients with different cancer types (22% genitourinary, 19% breast, 16% gastrointestinal, 15% lymphoma, 11% lung and 17% others), 51 patients (61%) had metastatic disease and 31 (31%) received chemotherapy alone. Main baseline cancer and VTE clinical characteristics did not differ between the 2 groups. Adherence rates to ITAC-CPGs was significantly higher in the AlloTC-MCP group (100% (M0), 72% (M3) and 68% (M6)) compared with the control group (84% (M0), 8% (M3) and 16% (M6)). Quality of Life (QoL) was significantly improved in the AlloTC-MCP group 6 months after inclusion. CONCLUSION: The "AlloTC-MCP" was associated with improved adherence to ITAC-CPGs and merits further expansion.


Subject(s)
Neoplasms , Venous Thromboembolism , Anticoagulants , Humans , Neoplasms/complications , Neoplasms/therapy , Pilot Projects , Prospective Studies , Quality of Life , Risk Factors , Venous Thromboembolism/complications , Venous Thromboembolism/drug therapy
7.
J Immunother Cancer ; 9(6)2021 06.
Article in English | MEDLINE | ID: mdl-34083421

ABSTRACT

BACKGROUND: Head and neck squamous cell carcinomas (HNSCCs) are common malignancies caused by carcinogens, including tobacco and alcohol, or infection with human papillomavirus (HPV). Immune checkpoint inhibitors targeting the programmed cell death 1 (PD-1) pathway are effective against unresectable recurrent/metastatic HNSCC. Here, we explored the safety and efficacy of anti-PD-1 therapy in at-risk resectable HPV-positive and HPV-negative HNSCC in the neoadjuvant setting. METHODS: The phase I/II CheckMate 358 trial in virus-associated cancers assessed neoadjuvant nivolumab in patients with previously untreated, resectable HPV-positive or HPV-negative HNSCC. Patients received nivolumab 240 mg intravenously on days 1 and 15, with surgery planned by day 29. Safety/tolerability (primary endpoint) was assessed by monitoring adverse events (AEs) and surgical delays. Radiographic response was measured before surgery using RECIST v1.1, adapted for a single post-nivolumab evaluation. Pathologic specimens were examined for treatment response using immune-based criteria. RESULTS: From November 2015 to December 2017, 52 patients with AJCC (seventh edition) stage III-IV resectable HNSCC received neoadjuvant nivolumab (26 HPV-positive, 26 HPV-negative). Any-grade treatment-related AEs (TRAEs) occurred in 19 patients (73.1%) and 14 patients (53.8%) in the HPV-positive and HPV-negative cohorts, respectively; grade 3-4 TRAEs occurred in five (19.2%) and three patients (11.5%), respectively. No patient had a protocol-defined TRAE-related surgical delay (>4 weeks). Thirty-eight patients were reported as undergoing complete surgical resection, 10 had a planned post-nivolumab biopsy instead of definitive surgery due to a protocol misinterpretation, and four did not undergo surgery or biopsy, including two with tumor progression. Radiographic response rates in 49 evaluable patients were 12.0% and 8.3% in the HPV-positive and HPV-negative cohorts, respectively. There were no complete pathologic responses by site or central review in operated patients. Among 17 centrally evaluable HPV-positive tumors, one (5.9%) achieved major pathological response and three (17.6%) achieved partial pathologic response (pPR); among 17 centrally evaluable HPV-negative tumors, one (5.9%) achieved pPR. CONCLUSIONS: Neoadjuvant nivolumab was generally safe and induced pathologic regressions in HPV-positive (23.5%) and HPV-negative (5.9%) tumors. Combinatorial neoadjuvant treatment regimens, and continued postoperative therapy for high-risk tumors, are warranted in future trials to enhance the efficacy of this approach. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02488759; https://clinicaltrials.gov/ct2/show/NCT02488759.


Subject(s)
Head and Neck Neoplasms/drug therapy , Immune Checkpoint Inhibitors/administration & dosage , Nivolumab/administration & dosage , Papillomavirus Infections/drug therapy , Squamous Cell Carcinoma of Head and Neck/drug therapy , Administration, Intravenous , Adult , Aged , Aged, 80 and over , Female , Head and Neck Neoplasms/virology , Humans , Immune Checkpoint Inhibitors/adverse effects , Male , Middle Aged , Neoadjuvant Therapy , Nivolumab/adverse effects , Papillomavirus Infections/complications , Squamous Cell Carcinoma of Head and Neck/virology , Treatment Outcome , Whole Genome Sequencing
8.
Laryngoscope Investig Otolaryngol ; 5(1): 19-23, 2020 Feb.
Article in English | MEDLINE | ID: mdl-32128426

ABSTRACT

OBJECTIVE: Osteoradionecrosis (ORN) of the sphenoid is a rare but potentially lethal complication that can occur after irradiation of nasopharyngeal and clival malignancies. The objective of this study was to describe a multimodal treatment strategy tailored to the clinical signs and to the radiological extent of the disease, and to report on its preliminary results. METHODS: Retrospective monocentric study at a tertiary skull base center. Patients treated for a sphenoid ORN from January 2014 to August 2018 were identified and charts were retrospectively reviewed for demographics, histologic tumor type, previous treatments of the tumor, clinical signs at presentation, radiological data, treatment, and outcomes. Sphenoid ORN was treated by a combination of medical therapy, endovascular treatment, and/or surgery. The use of each of these therapeutic modalities was based on the extent of ORN and on the presenting signs. RESULTS: Seven patients were included: four patients underwent endovascular treatment with occlusion of the internal carotid artery, five patients underwent surgical debridement, and covering of the exposed bone by a local flap, seven patients received antibiotics (in combination with pentoxyphilline, tocopherol, and clodronate in one case). Three patients died after progression of the ORN. The global survival rate was 57% (4/7) with a mean follow-up of 24 months. In one case, ORN was treated successfully by medical treatment only, with a combination of antibiotics, pentoxyphilline, tocopherol, and clodronate. CONCLUSION: This retrospective study describes the results of a management strategy adapted to the extent of the disease in sphenoid ORN and based on medical therapy only, or on a combination of medical therapy, interventional radiology, and/or surgery. LEVEL OF EVIDENCE: 4.

9.
Clin Genitourin Cancer ; 18(4): 295-303.e3, 2020 08.
Article in English | MEDLINE | ID: mdl-31882335

ABSTRACT

BACKGROUND: Neuroendocrine carcinoma of the urinary bladder (NCUB) is rare, accounting for < 1% of bladder cancer cases, with scarce reported data available. MATERIALS AND METHODS: We retrospectively reviewed the data from patients with NCUB treated at French institutions. The objectives were to describe the patient characteristics, treatments received, and outcomes (ie, disease-free survival [DFS], progression-free survival, overall survival [OS]) and investigate the prognostic factors. RESULTS: From 1997 to 2017, we included 236 patients, 173 with early-stage NCUB and 63 with advanced-stage NCUB. For those with early-stage disease, the median DFS was better for the patients who had received cisplatin-based chemotherapy compared with carboplatin (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.1-3.46), with no difference found between the neoadjuvant and adjuvant settings (HR, 1.1; 95% CI, 0.61-1.97). The median OS was 36 months (95% CI, 29-43 months) for stage I and II, 26 months (95% CI, 18 months to not reached) for stage IIIA, 16 months (95% CI, 12-21 months) for stage IIIB. The HR for stage IIIB compared with stage I/II was 2.6 (95% CI, 1.5-4.4). The DFS at 6 months was associated with OS (HR, 7.8; 95% CI, 4.1-15.0). For patients with metastases at diagnosis who had received chemotherapy, the median progression-free survival was 9 months (95% CI, 8-11) for first-line cisplatin and 6 months (95% CI, 4-13 months) for carboplatin; the median OS was 13 months (95% CI, 9-15 months). A high-risk Bajorin score (HR, 11.5; 95% CI, 1.2-112.6) and the use of carboplatin (HR, 2.26; 95% CI, 1.03-4.96) were associated with worse outcomes. CONCLUSIONS: In early-stage disease, a shorter DFS was associated with worse OS, and the use of cisplatin was associated with better OS. For the patients with metastases at diagnosis, a high-risk Bajorin score and the use of carboplatin were associated with worse outcomes.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Neuroendocrine/drug therapy , Chemotherapy, Adjuvant/mortality , Neoadjuvant Therapy/mortality , Urinary Bladder Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Carboplatin/administration & dosage , Carcinoma, Neuroendocrine/secondary , Cisplatin/administration & dosage , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate , Urinary Bladder Neoplasms/pathology
11.
J Pediatr Hematol Oncol ; 40(6): 426-432, 2018 08.
Article in English | MEDLINE | ID: mdl-29642099

ABSTRACT

High-risk neuroblastoma is characterized by poor long-term survival, especially for very high-risk (VHR) patients (poor response of metastases after induction therapy). The benefits of a tandem high-dose therapy and hematologic stem cell reinfusion (HSCR) have been shown in these patients. Further dose escalation will be limited by toxicity. It is thus important to evaluate the efficacy and tolerability of the addition of new agents such as I-MIBG (131Iode metaiodobenzylguanidine) to be combined with high-dose therapy in the consolidation phase. We report the feasibility of busulfan/melphalan (BuMel) after I-MIBG therapy with HSCR in patients with refractory or relapsed metastatic neuroblastoma. From November 2008 to March 2015, 9 patients received BuMel after I-MIBG therapy and topotecan. The main toxicity was digestive with only 1 patient developing grade 4 sinusoidal obstructive syndrome. Seven patients are alive at a median follow-up of 25 months. Among them, 2 are in ongoing complete remission and 1 in ongoing stable disease. These results suggest that BuMel with HSCR can be administered safely 2 months after I-MIBG therapy associated with topotecan for VHR patients. This strategy will be compared with tandem high-dose chemotherapy (thiotepa and busulfan-melphalan), followed by HSCR in the upcoming SIOPEN VHR Neuroblastoma Protocol.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Hematopoietic Stem Cell Transplantation , Neuroblastoma/therapy , 3-Iodobenzylguanidine/administration & dosage , 3-Iodobenzylguanidine/adverse effects , Adolescent , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Busulfan/administration & dosage , Busulfan/adverse effects , Child , Child, Preschool , Female , France/epidemiology , Humans , Male , Melphalan/administration & dosage , Melphalan/adverse effects , Neoplasm Metastasis , Neuroblastoma/mortality , Neuroblastoma/pathology , Risk Factors , Topotecan/administration & dosage , Topotecan/adverse effects
12.
Support Care Cancer ; 26(3): 751-758, 2018 Mar.
Article in English | MEDLINE | ID: mdl-28920149

ABSTRACT

PURPOSE: The purpose of this study is to assess the efficacy of 153Sm-EDTMP (Quadramet®) in a clinical setting. METHODS: We have conducted a retrospective study of all consecutive patients (pts) treated with 153Sm-EDTMP for painful bone metastases. At each visit (before and after treatment), four parameters were collected: (i) pain assessment according to the 10-step visual analogue scale (VAS), (ii) sleep disturbance related to pain, (iii) dose of analgesic medication, and (iv) answer to the following closed question "Do you think you obtained a benefit from treatment?" Success of treatment was defined by the combination of these four parameters. RESULTS: Three hundred seventy consecutive 153Sm-EDTMP treatments for painful bone metastases were given. Patients had the following primary tumors: breast carcinoma (153), prostate carcinoma (155), lung carcinoma (27), or other cancers (35). Fifty-eight percent of the patients had received previous external osseous radiotherapy. Ninety-seven percent of the patients were treated with concomitant analgesics and 61% were treated with diphosphonates. A clinical benefit was described in 55.0% of cases at D30. Treatment was more effective in cases of breast and prostate cancers compared with other types of primary cancers. Patients described a benefit at D30 in 62, 58, 6, and 38% of cases of breast, prostate, lung, and other cancers. The subjective efficacy was accompanied by a decrease in analgesic intake in 35.0% of cases. CONCLUSION: 153Sm-EDTMP therapy is an effective supportive treatment in patients who suffer from bone metastases, especially in patients with breast or prostate cancer.


Subject(s)
Bone Neoplasms/secondary , Pain/drug therapy , Radioisotopes/therapeutic use , Samarium/therapeutic use , Adult , Aged , Aged, 80 and over , Bone Neoplasms/drug therapy , Female , Humans , Male , Middle Aged , Radioisotopes/pharmacology , Retrospective Studies , Samarium/pharmacology , Treatment Outcome
13.
Rev Prat ; 68(1): 52-55, 2018 Jan.
Article in French | MEDLINE | ID: mdl-30840388

ABSTRACT

Medical treatment of metastatic kidney cancer: targeting the tumor micro-environment. Metastatic kidney cancer has a poor prognosis. Progress has been made in recent years with the development of drugs targeting the tumor microenvironment, namely angiogenesis and immune infiltrate. First-line drugs inhibit neo-angiogenesis and target the vascular endothelial growth factor receptor. Nivolumab is an anti-PD1 human monoclonal antibody that, by binding to its target, interrupts binding with its ligand PD-L1 and thus restores T-cell activation and destroys the tumor cell. The median overall survival of patients is about 2 years.


Traitements médicaux des cancers du rein métastatiques : le ciblage de l'environnement tumoral. Le cancer du rein métastatique a un pronostic sombre. Des progrès ont néanmoins été réalisés au cours des dernières années avec le développement de médicaments ciblant le microenvironnement tumoral, à savoir la néo-angiogenèse et plus récemment l'infiltrat lymphocytaire. Les médicaments utilisés en première intention inhibent la néo-angiogenèse et ont pour cible le récepteur du vascular endothelial growth factor. Le nivolumab est un anticorps monoclonal humain anti-PD1 qui, en se fixant sur sa cible, interrompt la liaison avec son ligand PD-L1 et permet ainsi de restaurer l'activation du lymphocyte T et de détruire la cellule tumorale. La médiane de survie globale des patients est d'environ 2 ans.


Subject(s)
Immunotherapy , Kidney Neoplasms , Antibodies, Monoclonal , Humans , Kidney Neoplasms/pathology , Kidney Neoplasms/therapy , Nivolumab , Tumor Microenvironment , Vascular Endothelial Growth Factor A
14.
Rare Tumors ; 9(3): 7074, 2017 10 03.
Article in English | MEDLINE | ID: mdl-29081928

ABSTRACT

Primary adenocarcinoma of the seminal vesicle is a rare condition with only about 60 cases described in the literature. The unusual characteristics of this disease makes diagnosis difficult and treatment strategies differ as there are no specific guidelines available. This report presents a case of adenocarcinoma of the seminal vesicle with lung metastases in which surgical and chemotherapeutic treatments have been carried out. The MVAC dose dense regimen following local resection seems effective in this scenario and may be used in the treatment of this disease.

15.
J Nucl Med ; 58(7): 1045-1053, 2017 07.
Article in English | MEDLINE | ID: mdl-28254869

ABSTRACT

See an invited perspective on this article on page 1043.This multicenter phase II study investigated a selective radiotherapy dose increase to tumor areas with significant 18F-misonidazole (18F-FMISO) uptake in patients with non-small cell lung carcinoma (NSCLC). Methods: Eligible patients had locally advanced NSCLC and no contraindication to concomitant chemoradiotherapy. The 18F-FMISO uptake on PET/CT was assessed by trained experts. If there was no uptake, 66 Gy were delivered. In 18F-FMISO-positive patients, the contours of the hypoxic area were transferred to the radiation oncologist. It was necessary for the radiotherapy dose to be as high as possible while fulfilling dose-limiting constraints for the spinal cord and lungs. The primary endpoint was tumor response (complete response plus partial response) at 3 mo. The secondary endpoints were toxicity, disease-free survival (DFS), and overall survival at 1 y. The target sample size was set to demonstrate a response rate of 40% or more (bilateral α = 0.05, power 1-ß = 0.95). Results: Seventy-nine patients were preincluded, 54 were included, and 34 were 18F-FMISO-positive, 24 of whom received escalated doses of up to 86 Gy. The response rate at 3 mo was 31 of 54 (57%; 95% confidence interval [CI], 43%-71%) using RECIST 1.1 (17/34 responders in the 18F-FMISO-positive group). DFS and overall survival at 1 y were 0.86 (95% CI, 0.77-0.96) and 0.63 (95% CI, 0.49-0.74), respectively. DFS was longer in the 18F-FMISO-negative patients (P = 0.004). The radiotherapy dose was not associated with DFS when adjusting for the 18F-FMISO status. One toxic death (66 Gy) and 1 case of grade 4 pneumonitis (>66 Gy) were reported. Conclusion: Our approach results in a response rate of 40% or more, with acceptable toxicity. 18F-FMISO uptake in NSCLC patients is strongly associated with poor prognosis features that could not be reversed by radiotherapy doses up to 86 Gy.


Subject(s)
Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/radiotherapy , Dose Fractionation, Radiation , Lung Neoplasms/metabolism , Lung Neoplasms/radiotherapy , Misonidazole/analogs & derivatives , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Female , France , Humans , Lung Neoplasms/diagnostic imaging , Male , Middle Aged , Misonidazole/pharmacokinetics , Observer Variation , Radiopharmaceuticals/pharmacokinetics , Reproducibility of Results , Sensitivity and Specificity , Survival Rate , Treatment Outcome , Tumor Hypoxia/radiation effects
16.
Radiat Prot Dosimetry ; 173(4): 395-404, 2017 Apr 15.
Article in English | MEDLINE | ID: mdl-26940442

ABSTRACT

The objective of the present multicentric phase II study (MIITOP) was to determine the response rate, survival and toxicity of tandem infusions of 131I-meta-iodobenzylguanidine (mIBG) and topotecan in children with relapsed/refractory neuroblastoma. High-dose 131I-mIBG therapy programme requires a deal of planning, availability of hospital resources and the commitment of individuals with training and expertise in multiple disciplines. Here in the present study, procedures and the results of patient's dosimetry, as well as family and worker's exposures, were reported for the patients treated in Lille. A total of 15 children were treated with 131I-mIBG between 2009 and 2011 according to the MIITOP protocol. High activity of 131I-mIBG (444 MBq kg-1) was administered on Day 0. In vivo dosimetry was used to calculate a second activity, to be given on Day 21, to obtain a total whole body absorbed dose of 4 Gy. Family and worker's exposures were performed too. The injected activity by treatment was from 703 to 11470 MBq. Total whole body absorbed dose by patient ranged from 2.74 to 5.2 Gy. Concerning relatives, whole body exposure ranged from 0.018 to 2.8 mSv. The mean whole body exposure of the radiopharmacist was 4.4 nSv MBq-1, and the mean exposure of fingers ranged from 0.18 to 0.24 µSv MBq-1 according to each finger. The mean whole body exposure was 33.6 and 20.2 µSv d-1 per person, for night nurses and day nurses, respectively. Exposure of doctors was less than 5 µSv d-1. Under strict radiation protection precautions, this study shows the feasibility of high-activity 131I-mIBG therapy in France.


Subject(s)
3-Iodobenzylguanidine/therapeutic use , Caregivers , Iodine Radioisotopes/therapeutic use , Neuroblastoma/radiotherapy , Radiation Exposure , Adult , Child , Female , France , Humans , Male , Neoplasm Recurrence, Local , Neuroblastoma/drug therapy , Radiometry , Topoisomerase I Inhibitors/therapeutic use , Topotecan/therapeutic use
17.
Clin Genitourin Cancer ; 15(3): e469-e476, 2017 06.
Article in English | MEDLINE | ID: mdl-27964892

ABSTRACT

BACKGROUND: A high neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation and is associated with poor survival in localized or metastatic cancer. This study assessed the prognostic value of NLR after first-line chemotherapy (CT) in patients with metastatic urothelial carcinoma (mUC). PATIENTS AND METHODS: Two hundred eighty consecutive patients treated with first-line platinum-based CT at 4 centers in France and Turkey between 2002 and 2014 were included. The association of NLR and Memorial Sloan Kettering Cancer Center (MSKCC) scores with overall survival (OS) and progression-free survival (PFS) was determined by univariate Cox models. RESULTS: Median OS was 10.6 months (follow-up, 42.8 months). In univariate analysis, high NLR was associated with worse OS (hazard ratio [HR] for death = 1.36; 95% confidence interval [CI], 1.23-1.51; P < .0001); the result was similar after adjustment for MSKCC prognostic group (HR = 1.28; 95% CI, 1.14-1.43; P < .0001). Low NLR was associated with longer PFS (HR = 1.18; 95% CI, 1.05-1.33; P < .005). When NLR was divided in terciles, OS in the lowest tercile (NLR 0.6-2.78) was 12.4 to 16.6 (median, 13.4) months versus 5.3 to 9.9 (median, 7.3) months in the highest tercile (NLR 4.70-48.9) (P = .001). Similar trends were observed for PFS (5.6-8.9 [median, 7.6] months vs. 3.1-5.7 [median, 4.8] months) in patients with NLR values in the lowest versus highest tercile, respectively (P = .021). CONCLUSION: High pre-CT NLR was an independent prognostic factor for poor OS and PFS in mUC patients. The prognostic value of NLR, as either a continuous or categorical variable, compared favorably with MSKCC score but was easier to assess and monitor.


Subject(s)
Biomarkers, Tumor/blood , Carcinoma, Transitional Cell/surgery , Neutrophils/cytology , Urologic Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Transitional Cell/blood , Carcinoma, Transitional Cell/mortality , Female , France , Humans , Leukocyte Count , Lymphocyte Count , Male , Middle Aged , Odds Ratio , Prognosis , Retrospective Studies , Survival Analysis , Turkey , Urologic Neoplasms/blood , Urologic Neoplasms/mortality
18.
Pathol Oncol Res ; 23(1): 139-144, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27605003

ABSTRACT

Administration of cytotoxic chemotherapy for patients with metastatic cancer and poor performance status is a daily clinical challenge. Guidelines only help to select a therapeutic regimen but do not offer a clear response whether or not the patients should be treated. We performed a prospective analysis in 139 metastatic patients with performance status > 1 according to the Eastern Cooperative Oncology Group scale. A decision was considered correct if patients treated with a medical anticancer treatment lived over 3 months or alternatively patients not treated had a survival under 3 months. The predominant tumor type was non-small cell lung cancer. Patients were chemotherapy naive in 87 cases (63 %). A new line of medical anticancer treatment was started in 107 cases (77 %). The median survival of the study population was 11 weeks (range, 1-53). 84 patients (60 %) died within 3 months while 55 patients (40 %) lived more than 3 months after decision. Treatment decisions were considered as appropriate in 81 cases (58 %). No patient was considered as undertreated. The analysis by pathology allowed to identify pathologies where decisions were correct in the majority of the cases (renal, urothelial and small cell lung cancers), pathologies where appropriate and inappropriate decisions were balanced (prostate, ovarian and breast cancers) and pathologies where decisions for treatment were excessive (non-small cell lung cancer and unknown primary). This prospective study was conducted as part of the evaluation of professional practices in our department. Administration of a medical anticancer treatment validated with patients with good performance status may be harmful for patients with poor performance status. The findings resulted in recommendations for daily practice in order to help physicians, especially for the "don't go" decisions. Until the identification of new prognostic factors for survival and/or the development of therapies making sensitive currently chemoresistant diseases, the initiation of a medical anticancer treatment outside standard situations should result from a consensual decision team or the inclusion in a clinical trial.


Subject(s)
Antineoplastic Agents/therapeutic use , Neoplasm Metastasis/drug therapy , Neoplasm Metastasis/pathology , Neoplasms/drug therapy , Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prognosis , Prospective Studies
19.
Bull Cancer ; 103(5): 444-54, 2016 May.
Article in French | MEDLINE | ID: mdl-26987841

ABSTRACT

Methotrexate represents the standard intrathecal treatment of breast cancer meningeal carcinomatosis. However, its optimal schedule remains undefined. The aim of the present study was to evaluate results obtained with the methotrexate schedule used in Saint-Louis hospital (Paris). Patients followed in Saint-Louis hospital for breast cancer and who received intrathecal methotrexate were included in this retrospective monocentric study. Intrathecal treatment received contained methotrexate 12 mg/day (days: 1-5) and then 15 mg/week until progression or toxicity. Between 2003 and 2015, 41 patients were included. Primitive tumours were RH+/HER2-, HER2+ and triple-negative in respectively 66%, 14%, 5% and 15% of patients, 22% of them had meningeal carcinomatosis as metastatic disease initial manifestation. Objective response rate was 54%, median overall survival was 4.0 mois [CI 95%: 3-7.3] and 1-year survival rate was 15.2% (11.4%, 50% et 0% in RH+/HER2-, HER2+ and triple-negative subgroups; HR=0.45 [0.21-0.97] between HER2+ and RH+/HER2-). In univariate analysis, prognostic factors were brain involvement (p=0.049), initial cerebrospinal fluid protein level (p=0.0002) and concomitant systemic treatment received (p=0.049). This intrathecal methotrexate schedule demonstrates a similar median overall survival as the one obtained with a dose-dense schedule and an improved quality of life. Nevertheless, as the objective response and 1-year survival rates are slightly inferior, a dose-dense schedule remains still preferred in HER2+ patients or in those harboring a mainly meningeal progression.


Subject(s)
Antimetabolites, Antineoplastic/administration & dosage , Breast Neoplasms/pathology , Meningeal Carcinomatosis/drug therapy , Meningeal Carcinomatosis/secondary , Methotrexate/administration & dosage , Adult , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/adverse effects , Arachnoiditis/chemically induced , Breast Neoplasms/chemistry , Breast Neoplasms/mortality , Clinical Protocols , Drug Administration Schedule , Female , Humans , Injections, Spinal , Meningeal Carcinomatosis/etiology , Meningeal Carcinomatosis/mortality , Methotrexate/adverse effects , Middle Aged , Paris , Prognosis , Retrospective Studies , Survival Rate , Time Factors , Triple Negative Breast Neoplasms/chemistry , Triple Negative Breast Neoplasms/mortality , Triple Negative Breast Neoplasms/pathology
20.
J Pediatr Hematol Oncol ; 38(4): e151-3, 2016 05.
Article in English | MEDLINE | ID: mdl-26907648

ABSTRACT

Wilms tumor is the most common renal tumor in children, and the 5-year survival rate is approximately 85%. The majority of relapses occur in the lung, tumor bed, and liver within 2 years of diagnosis. In this study, we describe an unusual late tumor recurrence that occurred 9.5 years after the primary diagnosis. The patient presented with a slow growing cervical lymphadenopathy. The recurrent tumor showed the same histologic features as the original tumor. The patient was treated with surgery and radiotherapy without chemotherapy. The patient remained disease free 15 months after treatment. The possible effect of treatment and other mechanisms of this late relapse are discussed.


Subject(s)
Recurrence , Wilms Tumor , Adolescent , Female , Humans , Kidney Neoplasms , Lymphadenopathy/diagnosis , Lymphadenopathy/etiology , Time Factors , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/etiology , Wilms Tumor/radiotherapy , Wilms Tumor/surgery
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