[Oncology in French Guiana: A challenge to win]. / La cancérologie en Guyane : un défi à gagner.

French Guiana is an equatorial, multicultural, overseas territory in South America. The region is unique: a wealthy country with a universal healthcare system, but significant poverty, which bears little resemblance to its neighbors Brazil and Suriname. Cancer is the second leading cause of death. The incidence of cancer is lower than in France, stages are generally more advanced and the prognosis worse. To date, oncology has been organized through a joint venture between local institutions and healthcare professionals and a cancer center in mainland France, in line with the recommendations of the Institut National du Cancer. The implementation of a medical project and a complete medical studies curriculum in French Guiana is a tremendous opportunity for the development of oncology. The main challenges are consolidating medical care for patients, quality control, genetic oncology, molecular biology, implementation of radiotherapy and nuclear medicine, clinical and translational research, and teaching programs. Working in oncology in French Guiana is exciting because of the scientific interest (particular characteristics of cancers, notably the role of viral or micro-organism-induced carcinogenesis, genetic factors in these populations with African and Asian roots, and the importance of a public health policy) and human interest (patients from different cultures; all of them bring original approaches to health and illness that need to be deciphered in order to offer quality care). This requires the support of healthcare professionals who are enthusiastic about this unique adventure.

Adult T-cell leukemia and lymphoma in French Guiana: a retrospective analysis with real-life data from 2009 to 2019.

Background: Adult T-cell leukemia/lymphoma (ATL), one of the most aggressive cancers in the world, occurs in 5% of the 10 million people living with HTLV-1 worldwide. French Guiana, a French overseas territory in South America, is one of the highest endemic areas of HTLV-1 worldwide. Here, we describe the demographic and clinical characteristics and outcome of ATL in this area. Methods: We retrospectively collected data from all patients diagnosed between 2009 and 2019. Patients were distributed according to Shimoyama's classification. Prognostic factors were explored through univariate analysis. Findings: Over the 10-year study period, 41 patients with a median age of 54 years at diagnosis were identified, among whom 56% were women. Sixteen (39%) patients were Maroons, a cultural group descendant of the runaway enslaved Africans from former Dutch Guiana. Among the study population, 23 (56%) had an acute type, 14 (34%) a lymphoma type, and one and one chronic and primary cutaneous tumour, respectively. First-lines of treatment included either chemotherapy or Zidovudine combined with pegylated interferon alpha. The 4-year overall survival was 11.4% for the entire population with 0% and 11% for lymphoma and acute forms, respectively. The median progression-free survival was 93 and 115 days for the acute and lymphoma groups (p = 0.37), respectively. Among the twenty-nine patients who died, 8 (28%) died of toxicity, 7 (24%) died of disease progression and the cause of death remained unknown in 14 (48%) patients. Due to the overall poor prognosis, no significant prognostic factors could be identified. Interpretation: This study provides real-life data from ATL patients in French Guiana, a remote territory in a middle-income region. Patients, mostly Maroons, presented with a younger age and the prognosis was worse than expected compared to Japanese patients. Funding: None.

[Gender and sexual minorities: Unknowns in the cancer care pathway]. / Minorités de genre et minorités sexuelles : des inconnus du parcours de soins en cancérologie.

The French National Cancer Institute, in its ten-year roadmap, has defined an axis 4: "ensuring that progress benefits all". The Association francophone sur les soins oncologiques de support wished to take stock of cancer care for gender and sexual minorities. The authors, who have a sociological and oncological background, have gathered the main data from the French-language literature limited to sociological aspects. They address the definitions of sexual orientation, identity and practice, gender identity, expression and assignment, and the issue of intersex. They report on the concrete problems from patients' narratives. Little research has been done on cancer patients. Studies on children and young adolescents focus on other issues (harassment, discrimination, dropping out of school); those on the older persons show the invisibility of the issue. For adults, the organization of the care process is obscured by a purely psychiatric and technical medical approach. The relationship of trust is not established, and the terms and views used lead to delays and breaks in care. To remedy these shortcomings, the authors suggest that training efforts be made (for patients and caregivers), that community associations be supported, and that sociological and medical research be carried out, considering an approach by cancer pathology as well as by sexual or gender minority groups.

Anti-neoplastic agents for patients on peritoneal dialysis: A systematic review.

BACKGROUND: There is no clear consensus on the administration of anti-neoplastic agents to patients on peritoneal dialysis. Dose adjustments to prevent serious adverse events are still not established. Thus, the aim of this study was to systematically review current evidence on the use of systemic oncology therapies in peritoneal dialysis. METHODS: A systematic review was conducted using PubMed, Scopus, and Cochrane. All relevant data was collected, including clinical and pharmacokinetic parameters, with comparison to subjects with normal renal function. RESULTS: Sixteen studies were included. All were case reports. Eighteen types of anti-cancer drugs were reviewed. Multiple adverse events and altered pharmacokinetics were reported. CONCLUSION: Data concerning the use of anti-neoplastic drugs in patients on peritoneal dialysis are still sparse. The elimination of anti-cancer agents seems often altered in such patients, resulting in serious adverse events. Based on the available evidence, we suggest the need for dose adjustment of each drug.

Curative Treatment for Muscle Invasive Bladder Cancer in Elderly Patients: A Systematic Review.

CONTEXT: The incidence of muscle invasive bladder cancer (MIBC) increases with age. With increased life expectancy the number of elderly MIBC patients is expected to increase. Existing guidelines on management of MIBC do not preclude curative treatments for elderly patients. However, it is necessary to assess the risks and benefits of a treatment to avoid overtreatment that results in decreased health-related quality of life without prolonging survival. OBJECTIVE: To report on overall survival (OS), cancer specific survival (CSS), and morbidity after curative treatment in elderly patients, defined as age >70 yr, with nonmetastatic MIBC and to compare this with the outcome of younger MIBC patients. EVIDENCE ACQUISITION: A systematic review was performed using Medline, PubMed, and Embase databases. Articles were included if they addressed one of the three research questions: Only articles including >100 patients and with a clear age-stratification were included. EVIDENCE SYNTHESIS: Forty-two articles were retrieved for review. No article directly addressed the use of geriatric assessment. OS and CSS worsen significantly with age both after radical cystectomy and radiotherapy regimens. While POM significantly increases with age, morbidity seems comparable between younger and older patients. CONCLUSIONS: Although a proportion of elderly patients with MIBC will benefit from curative treatment, we observed worse OS, CSS, and POM with age. The impact of age on late morbidity is less clear. Prospective studies evaluating geriatric assessments are critically needed to optimize MIBC management in the elderly. PATIENT SUMMARY: We performed a systematic review to evaluate the outcome and complication rate in elderly patients with muscle invasive bladder cancer. We observed that overall survival and cancer specific survival significantly decrease and perioperative mortality significantly increases with age. The impact of age on late morbidity is less clear. There is a need for geriatric assessments to select those patients that will benefit from curative treatment.

Role of Geriatric Oncologists in Optimizing Care of Urological Oncology Patients.

CONTEXT: Urological cancers are common. Since the median age of diagnosis is 60-70 yr, many patients require geriatric as well as urological evaluation if treatment is to be tailored to individual health status including comorbidities and frailty. OBJECTIVE: To review the most important features of geriatric assessment and its expected benefits. We also consider ways in which collaboration between urologists and geriatricians and geriatric teams can benefit patient well-being. EVIDENCE ACQUISITION: Members of a multidisciplinary International Society of Geriatric Oncology task force reviewed articles published in 2010-2017 using search terms relevant to urological cancers, the elderly, and geriatric evaluation. The final manuscript reflects their expert consensus. EVIDENCE SYNTHESIS: Elderly patients should be managed according to their individual health status and not according to age. As a first step, screening for cognitive impairment is mandatory to establish patient competence in making decisions. Initial evaluation of health status should use a validated screening tool, the G8 screening tool being generally preferred. Abnormal scores on the G8 should lead to a geriatric assessment that evaluates comorbid conditions and functional, nutritional, mental, and medicosocial status. When patients are frail or disabled or have severe comorbidities, comprehensive geriatric assessment is required. Diagnosis of health status impairment shows the need for geriatric interventions. This overall approach is realistic in the setting of a department of urological oncology and given the involvement of a multidisciplinary team including trained nurses and other professionals and collaboration with geriatricians. Mutual education and support of all those involved in managing elderly urological cancer patients is the key to effective care. CONCLUSIONS: Advances in geriatric evaluation and cancer treatment are contributing to more appropriate management of elderly patients with urological cancers. Better understanding of the role of all participants and professional collaboration are vital to the individualization of care. PATIENT SUMMARY: Many patients with urological cancers are elderly. In those physically fit, treatment should generally be the same as that in younger patients. Some elderly cancer patients are frail and have other medical problems. Treatment in individual patients should be based on health status and patient preference.

Management of Prostate Cancer in Elderly Patients: Recommendations of a Task Force of the International Society of Geriatric Oncology.

CONTEXT: Prostate cancer is the most frequent male cancer. Since the median age of diagnosis is 66 yr, many patients require both geriatric and urologic evaluation if treatment is to be tailored to individual circumstances including comorbidities and frailty. OBJECTIVE: To update the 2014 International Society of Geriatric Oncology (SIOG) guidelines on prostate cancer in men aged >70 yr. The update includes new material on health status evaluation and the treatment of localised, advanced, and castrate-resistant disease. DATA ACQUISITION: A multidisciplinary SIOG task force reviewed pertinent articles published during 2013-2016 using search terms relevant to prostate cancer, the elderly, geriatric evaluation, local treatments, and castration-refractory/resistant disease. Each member of the group proposed modifications to the previous guidelines. These were collated and circulated. The final manuscript reflects the expert consensus. DATA SYNTHESIS: Elderly patients should be managed according to their individual health status and not according to age. Fit elderly patients should receive the same treatment as younger patients on the basis of international recommendations. At the initial evaluation, screening for cognitive impairment is mandatory to establish patient competence in making decisions. Initial evaluation of health status should use the validated G8 screening tool. Abnormal scores on the G8 should lead to a simplified geriatric assessment that evaluates comorbid conditions (using the Cumulative Illness Score Rating-Geriatrics scale), dependence (Activities of Daily Living) and nutritional status (via estimation of weight loss). When patients are frail or disabled or have severe comorbidities, a comprehensive geriatric assessment is needed. This may suggest additional geriatric interventions. CONCLUSIONS: Advances in geriatric evaluation and treatments for localised and advanced disease are contributing to more appropriate management of elderly patients with prostate cancer. A better understanding of the role of active surveillance for less aggressive disease is also contributing to the individualisation of care. PATIENT SUMMARY: Many men with prostate cancer are elderly. In the physically fit, treatment should be the same as in younger patients. However, some elderly prostate cancer patients are frail and have other medical problems. Treatment in the individual patient should be based on health status and patient preference.

Performance of Four Frailty Classifications in Older Patients With Cancer: Prospective Elderly Cancer Patients Cohort Study.

Purpose Frailty classifications of older patients with cancer have been developed to assist physicians in selecting cancer treatments and geriatric interventions. They have not been compared, and their performance in predicting outcomes has not been assessed. Our objectives were to assess agreement among four classifications and to compare their predictive performance in a large cohort of in- and outpatients with various cancers. Patients and Methods We prospectively included 1,021 patients age 70 years or older who had solid or hematologic malignancies and underwent a geriatric assessment in one of two French teaching hospitals between 2007 and 2012. Among them, 763 were assessed using four classifications: Balducci, International Society of Geriatric Oncology (SIOG) 1, SIOG2, and a latent class typology. Agreement was assessed using the κ statistic. Outcomes were 1-year mortality and 6-month unscheduled admissions. Results All four classifications had good discrimination for 1-year mortality (C-index ≥ 0.70); discrimination was best with SIOG1. For 6-month unscheduled admissions, discrimination was good with all four classifications (C-index ≥ 0.70). For classification into three (fit, vulnerable, or frail) or two categories (fit v vulnerable or frail and fit or vulnerable v frail), agreement among the four classifications ranged from very poor (κ ≤ 0.20) to good (0.60 < κ ≤ 0.80). Agreement was best between SIOG1 and the latent class typology and between SIOG1 and Balducci. Conclusion These four frailty classifications have good prognostic performance among older in- and outpatients with various cancers. They may prove useful in decision making about cancer treatments and geriatric interventions and/or in stratifying older patients with cancer in clinical trials.

First-line treatment in senior adults with metastatic castration-resistant prostate cancer: A prospective international registry.

AIMS: To compare the efficacy and tolerability of taxane and nontaxane therapy in senior adults with chemonaïve metastatic castration-resistant prostate cancer (mCRPC), and examine the effect of patient health status on outcomes. PATIENTS AND METHODS: Between 2009 and 2011, 333 patients aged≥70 years with mCRPC were enrolled in a prospective international registry. Patients were categorized as having received taxane-based or nontaxane therapy, and classified as fit, vulnerable, frail, or terminal, according to investigator judgement or International Society of Geriatric Oncology guidelines. Efficacy measures included overall survival (OS) and progression-free survival. Grade 3/4 toxicities were recorded. Predictors of OS were identified using multivariate Cox regression. RESULTS: The proportions of fit/vulnerable/frail patients were 65%/14%/17% (International Society of Geriatric Oncology), and 39%/43%/17% (investigator). In single-factor analyses, taxane therapy improved OS (hazard ratio [95%CI] = 0.53 [0.30-0.93]; P = 0.027) and progression-free survival (hazard ratio [95% CI] = 0.55 [0.40-0.76]; P<0.001) vs. nontaxane therapy. Patients with frailty also benefited from taxane therapy (adapted regimen in 52%). In multivariate analysis, taxanes improved OS even with poor prognostic factors present (P = 0.017); age was unrelated to prognosis. Taxane therapy was well tolerated; most common grade 3/4 toxicities (taxane vs. nontaxane) were fatigue (17% vs. 4%), nausea/vomiting (14% vs. 5%) and neutropenia (10% vs. 1%). CONCLUSIONS: The results of this nonrandomized, observational study suggest that first-line taxane therapy may benefit senior adults with mCRPC more than alternative therapies. Treatment decisions should not be based on chronological age.

Management of prostate cancer in older patients: updated recommendations of a working group of the International Society of Geriatric Oncology.

In 2010, the International Society of Geriatric Oncology (SIOG) developed treatment guidelines for men with prostate cancer who are older than 70 years old. In 2013, a new multidisciplinary SIOG working group was formed to update these recommendations. The consensus of the task force is that older men with prostate cancer should be managed according to their individual health status, not according to age. On the basis of a validated rapid health status screening instrument and simple assessment, the task force recommends that patients are classed into three groups for treatment: healthy or fit patients who should have the same treatment options as younger patients; vulnerable patients with reversible impairment who should receive standard treatment after medical intervention; and frail patients with non-reversible impairment who should receive adapted treatment.

Randomized phase II study of nintedanib in metastatic castration-resistant prostate cancer postdocetaxel.

This open-label, phase II trial assessed the efficacy and safety of two doses of nintedanib, a triple angiokinase inhibitor targeting vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor signaling, in patients with metastatic castration-resistant prostate cancer (mCRPC) following progression on docetaxel-based regimens. Patients were randomized to nintedanib 150 mg (arm A, n=40) or 250 mg (arm B, n=41) twice daily for 6 months unless disease progression or adverse events (AEs) led to discontinuation. The primary endpoint was the prostate-specific antigen (PSA) response rate (confirmed PSA decline of ≥20% from baseline). Eighty-one patients were enrolled. The PSA response rate was 0% (0/32) in arm A versus 11.1% (4/36) in arm B (P=0.12); 5.6% of patients (2/36) in arm B showed a PSA reduction of at least 50%. In arm B, the rate of PSA increase was significantly decelerated on treatment versus before treatment (P=0.002). The median progression-free survival was 73.5 and 76.0 days for arm A and arm B, respectively (P=0.3). AEs included gastrointestinal disorders, asthenia, hypertension, and reversible elevated transaminases. The incidence of drug-related serious AEs (no drug-related deaths) was 20.0% (arm A) and 24.4% (arm B). The primary endpoint was not met. Nintedanib (250 mg) showed only modest activity with manageable AEs in patients with mCRPC post-docetaxel.

[Treatment of testicular cancer]. / Le traitement du cancer du testicule.

Germ-cell tumours (GCTs) are the most common type of cancer in young men. Since the late 1970s, disseminated GCT have been a paradigm for curable metastatic cancer and metastatic GCTs are highly curable with cisplatin-based chemotherapy followed by surgical resection of residual masses. Patients' prognosis is currently assessed using the International Germ-Cell Consensus Classification (IGCCC) and used to adapt the burden of chemotherapy. Approximately 20% of patients still do not achieve cure after first-line cisplatin-based chemotherapy, and need salvage chemotherapy (high dose or standard dose chemotherapy). Clinical stage I testicular cancer is the most common presentation and different strategies are proposed: adjuvant therapies, surgery or surveillance. During the last three decades, clinical trials and strong international collaborations lead to the development of a consensus in the management of GCTs.

Risk-adapted, dose escalation study of weekly docetaxel in the first-line treatment of elderly patients with advanced cancer.

OBJECTIVES: As a consequence of under-representation of elderly patients in clinical trials, the recommended dose of chemotherapy is often based on results observed in younger patients. We designed a risk-adapted, dose escalation study of weekly docetaxel in the first-line treatment of elderly patients with cancer in order to determine the optimal dose according to age, comorbidity and functional status. PATIENTS AND METHODS: Sixty-eight patients aged 70 or more were stratified into three risk groups according to a combination of age, performance status, and comorbidity. The study was conducted using a standard phase I design with sequential cohorts of patients receiving docetaxel at increasing doses in each risk group. RESULTS: The maximum tolerated dose was not reached in the intermediate-risk group and was 45mg/m(2)/week in the high-risk group. Because of a slow recruitment rate, it was not possible to conclude the trial in the good-risk category. Neutropenia, asthenia and diarrhea were the most frequently encountered severe toxicities. CONCLUSIONS: Docetaxel can be used at a dose of 40mg/m(2)/week as a first-line treatment for elderly patients with locally advanced or metastatic cancer without excessive toxicity. The risk groups defined in the study are not able to accurately distinguish between subgroups of patients with divergent toxicity profiles.

Sorafenib and sunitinib for elderly patients with renal cell carcinoma.

BACKGROUND: Sunitinib and sorafenib are small-molecule tyrosine kinase inhibitors with known antitumor activity in advanced renal cell carcinoma. MATERIALS AND METHODS: We retrospectively assess the response and tolerance of elderly patients with renal cell carcinoma to these two agents. Data of patients aged ≥70years receiving sorafenib or sunitinib at the Centre Léon Bérard were analyzed. Forty-eight patients received sorafenib or sunitinib as a first line treatment, 8 received sorafenib followed by sunitinib and 4 received the reverse sequence. Objective responses (ORs), stable disease (SD), toxicity, overall survival (OS) and progression-free survival (PFS) were reported. RESULTS: Sorafenib and sunitinib achieved similar OR+SD rates (79% vs. 71% respectively). Median PFS was 6months in first-line sorafenib treated patients and 5months in the sunitinib group. Median OS was 16months in first-line sorafenib-treated patients and 15months in the sunitinib group. In patients receiving sorafenib followed by sunitinib, median PFS was 11.5months, and median OS was 13.1months. With the reverse sequence, median PFS was 8.1months and median OS was 15months. Treatment modifications were more frequent in sunitinib-treated patients, in first or second line (75% vs. 50%). Limitations are the retrospective design of the study and the small number of patients. CONCLUSION: First-line sunitinib and sorafenib seem equally efficient in elderly patients treated for advanced renal carcinomas, but sunitinib is less well tolerated. Sequential treatment with sorafenib followed by sunitinib seems to be better tolerated. These results should be confirmed in a larger prospective study.

Retroperitoneal vascular surgery for the treatment of giant growing teratoma syndrome.

OBJECTIVE: To evaluate whether an aggressive surgical policy, which included vascular surgery with standard retroperitoneal lymph node dissection (RPLND), would be justified for managing bulky retroperitoneal growing teratoma syndrome (GTS). METHODS: Data were collected retrospectively from a series of 12 patients who, from 1992 to 2010, underwent radical RPLND for bulky GTS (retroperitoneal mass≥10 cm in diameter). For complete resection, vascular procedures and nephrectomy were performed. RESULTS: Median tumor diameter was 100 mm before and 140 mm (range 100-300) after chemotherapy. Two patients underwent iterative RPLND. In addition to RPLND, patients underwent aortic section with aortic anastomosis (n=6), inferior vena cava resection (n=3), both the latter and the former (n=1), and aortic graft with left nephrectomy (n=2). There were no operative deaths; 3 patients had complications (25%), but none were related to extended procedures. The median hospital stay was 15 days. Median follow up was 59 months (range 10-162). One patient died of metastatic cutaneous melanoma 112 months after RPLND, 10 patients survived and are disease-free, and one patient had a para-aortic recurrence. CONCLUSION: A 100% complete resection rate, long-term survival, no mortality, and acceptable morbidity were achieved when vascular surgery and left nephrectomy were combined with standard RPLND for bulky GTS.

Sarcoid-like granulomatosis and testicular germ cell tumor: the 'Great Imitator'.

OBJECTIVES: Only a few case reports and small case series of patients with sarcoidosis or sarcoid-like reaction and testicular germ cell tumors (GCT) have been reported in the literature. We performed a retrospective study of patients with testicular GCT managed at the Centre Léon-Bérard, who presented granulomatosis. METHODS: We performed a computerized search to identify all male patients with both a diagnosis of sarcoidosis or granuloma and testicular tumors seen at the Centre Léon-Bérard between 1992 and 2008. RESULTS: A total of 13 patients were identified among the 1,182 patients with testicular tumors. The median age at diagnosis of testicular GCT was 25.5 years. Six patients had stage I disease, 2 patients had stage IIb and 5 patients had stage III. Sarcoid-like granulomatosis was found in 9 patients at the time of initial diagnosis and in 4 patients during follow-up. Sarcoidosis presented mainly as pulmonary disease without severe organ involvement, with a benign evolution. CONCLUSION: We advise caution in the interpretation of clinical and histological findings in these patients. Sarcoid-like granulomatosis, a condition that can be combined with testicular cancer, should always be considered in the differential diagnosis of metastatic testicular tumors.

Results of combined treatment of anaplastic thyroid carcinoma (ATC).

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is among the most aggressive human malignancies. It is associated with a high rate of local recurrence and with poor prognosis. METHODS: We retrospectively reviewed 44 consecutive patients treated between 1996 and 2010 at Leon Berard Cancer Centre, Lyon, France. The combined treatment strategy derived from the one developed at the Institut Gustave Roussy included total thyroidectomy and cervical lymph-node dissection, when feasible, combined with 2 cycles of doxorubicin (60 mg/m2) and cisplatin (100 mg/m2) Q3W, hyperfractionated (1.2 Gy twice daily) radiation to the neck and upper mediastinum (46-50 Gy), and then four cycles of doxorubicin-cisplatin. RESULTS: Thirty-five patients received the three-phase combined treatment. Complete response after treatment was achieved in 14/44 patients (31.8%). Eight patients had a partial response (18.2%). Twenty-two (50%) had progressive disease. All patients with metastases at diagnosis died shortly afterwards. Thirteen patients are still alive. The median survival of the entire population was 8 months. CONCLUSION: Despite the ultimately dismal prognosis of ATC, multimodality treatment significantly improves local control and appears to afford long-term survival in some patients. There is active ongoing research, and results obtained with new targeted systemic treatment appear encouraging.

[High dose chemotherapy and germ cell tumor]. / Chimiothérapie intensive et autogreffe de cellules souches hématopoïétiques dans les tumeurs germinales.

Germ cell tumors are cured by cisplatin-based chemotherapy and secondary surgery. Patients with initial poor response to chemotherapy and relapsed disease patients have poor prognosis. Among different therapeutic approaches high dose chemotherapy with hematopoietic stem cell support has been studied. Despite the existence of a number of phase II trials and several well-conducted phase III trials, this approach is neither a standard nor an option in the setting of first line and first salvage treatment. A randomized phase III trial has recently been initiated and patients with relapsed disease should be offered to participate in the trial. Several selected indications could be discussed in further lines of treatment.

Targeted therapies and thyroid cancer: an update.

The treatment of metastatic, progressive thyroid cancer has evolved over recent years. New 'targeted' therapeutic approaches have been developed along with advances in the knowledge of thyroid carcinogenesis and the identification of tumor and endothelial targets. In recent years, results of targeted therapies have shown some benefit in refractory, progressive, differentiated, and medullary thyroid carcinomas but not, until recently, in undifferentiated thyroid carcinoma. We review here the different targeted therapies tested in thyroid cancers.