Local Treatment Of Metastases Research Articles

Long-term efficacy analysis of radiotherapy and local management of metastases in patients with newly diagnosed oligometastatic nasopharyngeal carcinoma: A prospective, single-arm, single-center clinical study

PurposeWe conducted a single-center, single-arm study (NCT 03129412) to prospectively analyze the long-term outcomes of newly diagnosed patients with oligometastatic nasopharyngeal carcinoma (NPC) who received radical radiotherapy and local treatment of metastases. Patients and methodsPatients who reached disease controll after platinum-based palliative chemotherapy continued to receive radical radiotherapy for the nasopharyngeal region and neck. Appropriate local treatments were selected to treat the metastatic lesions. The primary endpoint of this study was overall survival (OS) and the secondary endpoint was progression-free survival (PFS). ResultsFifty-one patients were included in the final analysis. During a median follow-up of 60 months, the median OS and PFS were 53.87 and 24.23 months, respectively. The 1-year, 3-year, and 5-year PFS and OS rates were 76.5 %, 38.1 %, and 31.8 % and 98 %, 75.4 %, 45.6 %, respectively. Both single and multivariate analysis indicated that maintenance therapy after radiotherapy could significantly increase PFS (36.43 vs. 16.1 months, P = 0.005). The OS of patients with single organ metastasis was significantly better than that of patients with double organ metastasis (P = 0.001). In addition, the number of metastatic organs also significantly affected PFS in the multifactor analysis. ConclusionPatients with newly diagnosed oligometastatic NPC can achieve long-term survival after receiving radical radiotherapy to the primary site and local treatment for metastases.

Lung Oligometastasis of Breast Cancer: Prospective Cohort Study of Treatment Strategies (SBP-06).

While local treatment of metastases is considered to be unrelated to prognosis, previous studies have suggested that local treatment of isolated lung metastases may have positive prognostic impact. We designed this prospective cohort study to investigate the clinical situation and its outcomes. We enrolled patients with fewer than 3 lung nodules suspected of being oligometastases after curative breast cancer surgery. Treatments, including local and systemic therapy, were selected by the physician and patient in consultation. The primary outcome was overall survival (OS); secondary outcomes were the efficacy and the safety of the surgery for lung oligometastases. Between May 2015 and May 2019, 14 patients were enrolled. Resection of lung nodules (metastasectomy) was performed in 11 (78.6%) of 14 patients, and one of these cases was diagnosed as primary lung cancer. Metastasectomies were all performed employing video-assisted thoracic surgery (VATS) without perioperative complications. Systemic therapies were administered to all patients except one. The respective 3-year and 5-year OS rates of patients with lung oligometastases were 91.6% and 81.5%, respectively. Progression occurred in 6 patients: 3 of the 10 with metastasectomy and all 3 without this surgical procedure. Lung metastasectomy was worthwhile as a diagnostic evaluation and may provide long-term benefit in some patients.

Impact of EDP-M on survival of patients with metastatic adrenocortical carcinoma: A population-based study

IntroductionHistorically, stage IV adrenocortical carcinoma (mACC) has a poor prognosis with a median overall survival (OS) of only 5 months. Based on the FIRM-ACT trial published in 2012, guidelines now advise first line systemic treatment with etoposide, cisplatin, doxorubicin and mitotane (EDP-M). The effect of EDP-M on patient survival in clinical practice in the Netherlands is unknown. MethodsThe data of all patients with mACC (2005–2020) were obtained from the Netherlands comprehensive cancer organization (IKNL). The effect of EDP-M on patient survival was assessed using Kaplan-Meier analysis and multivariate Cox regression analysis including clinical, therapy and tumor characteristics. ResultsIn total 167 patients with mACC were included. For patients diagnosed from 2014 onwards, EDP-M (in 22 patients (22%)) lead to a numerically but not statistically significant improved OS compared to those not receiving EDP-M (11.8 vs 5.6 months, p = 0.525). For systemic treatments, patients treated with mitotane only had the best 5-year OS (11.4%, p = 0.006) regardless of year of diagnosis. In multivariate Cox regression analysis EPD-M was not associated with OS; palliative adrenalectomy (HR: 0.26, p = <.001) and local treatment of metastases (HR: 0.35, p = 0.001) were associated with a better OS and a primary tumor Ki-67 index > 20% (HR: 2.67, p = 0.003) with a worse OS from 2014 onwards. Patients diagnosed before 2014 had a significantly poorer OS compared to from 2014 onwards (5-yr: 4.5 vs 8.4%, OS: 6.8 vs 8.3 months, p = 0.032). ConclusionOS for mACC in the Netherlands has improved in the last decade. Receiving EDP-M did not significantly improve OS for patients with mACC. The use of multimodality treatment including palliative adrenalectomy, mitotane and local treatment of (oligo-)metastases in appropriately selected patients has improved the OS for mACC patients since 2014.

French AFU Cancer Committee Guidelines - Update 2022-2024: management of kidney cancer

To update the recommendations for the management of kidney cancers. A systematic review of the literature was conducted from 2015 to 2022. The most relevant articles on the diagnosis, classification, surgical treatment, medical treatment and follow-up of kidney cancer were selected and incorporated into the recommendations. Therefore, the recommendations were updated while specifying the level of evidence (high or low). The gold standard for the diagnosis and evaluation of kidney cancer is contrast-enhanced chest and abdominal CT. MRI and contrast-enhanced ultrasound are indicated in special cases. Percutaneous biopsy is recommended in situations where the results will influence the therapeutic decision. Renal tumours should be classified according to the pTNM 2017 classification, the WHO 2022 classification and the ISUP nucleolar grade. Metastatic kidney cancer should be classified according to the IMDC criteria. Partial nephrectomy is the gold standard treatment for T1a tumours and can be performed by an open approach, by laparoscopy or by robot-guidance. Active surveillance of tumours less than 2cm in size can be considered regardless of the patient's age. Ablative therapies and active surveillance are options in elderly patients with comorbidity. T1b tumours should be treated by partial or radical nephrectomy depending on the complexity of the tumour. Radical nephrectomy is the first-line treatment for locally advanced cancers. Adjuvant treatment with pembrolizumab should be considered in patients at intermediate and high risk for recurrence after nephrectomy. In metastatic patients: Immediate cytoreductive nephrectomy may be offered to oligometastatic patients in combination with local treatment of metastases if this can be complete and delayed cytoreductive nephrectomy can be proposed for patients with a complete response or a significant partial response. Medical treatment should be proposed as first-line therapy for patients with a poor or intermediate prognosis. Surgical or local treatment of metastases can be proposed in case of single or oligo-metastases. The recommended first-line drugs for metastatic patients with clear cell renal carcinoma are the combinations axitinib/pembrolizumab, nivolumab/ipililumab, nivolumab/cabozantinib and lenvatinib/pembrolizumab. Cabozantinib is the recommended first-line treatment for patients with metastatic papillary carcinoma. Cystic tumours should be classified according to the Bosniak classification. Surgical removal should be proposed as a priority for Bosniak III and IV lesions. It is recommended that patient monitoring be adapted to the aggressiveness of the tumour. These updated recommendations are a reference that will allow French and French-speaking practitioners to improve kidney cancer management.

Néoplasies neuro-endocrines broncho-pulmonaires primitives : tumeurs carcinoïdes et carcinomes neuro-endocrines à grandes cellules

Primary pulmonary neuroendocrine neoplasms comprise several distinct clinical entities, corresponding to four main histological subtypes: well differentiated neuroendocrine tumors including typical carcinoid tumors, of low grade malignancy and atypical carcinoids of intermediate grade malignancy; and neuro-endocrine carcinomas with either small or large cells, of high grade malignancy.The pre-treatment workup of carcinoid tumors relies on specific recommendations. Any clinical suspicion of an associated functional syndrome must be confirmed by the appropriate blood dosages.In case of metastatic carcinoid tumor, management relies on the control of a possible secretory syndrome, in addition to the oncological treatment, based on the evaluation of tumor progression, with several opportunities: close follow-up, local treatment of metastases, treatment with somatostatin analogues, everolimus, or chemotherapy for tumor with high aggressiveness. Peptide receptor radionuclide therapy with 177Lu-DOTATATE in patients with somatostatin receptor-expressing neuroendocrine tumors is an interesting option not yet validated for routine use.In case of advanced, metastatic large-cell neuroendocrine carcinoma, platinum and etoposide combination is generally used in front line. However, for tumors that express RB or harbor KRAS or STK11 mutations, platinum and gemcitabine or platinum and taxane combination may be used. No established second line is available, but treatments used in NSCLC can be suggested, except pemetrexed.1877-1203/© 2022 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Long-term survival after sequential local treatments for oligometastatic esophageal squamous cell carcinoma: A case report.

Patients with metastatic esophageal cancer generally have a poor prognosis. In patients with oligometastatic disease (OMD), local treatment of metastases may improve overall survival (OS). This case report describes a 57-year-old female with a cT4bN2M1 mid-esophageal squamous cell carcinoma with ingrowth in the aorta and pathologic para-aortic lymph node metastases in the left thorax (i.e. synchronous OMD). The patient first underwent a robot-assisted thoracoscopic para-aortic lymph node dissection (R1, aorta). After response to definitive chemoradiotherapy (ycT4aN1), a salvage robot-assisted minimally-invasive esophagectomy was performed (ypT0N1, R0). During follow-up, metastasectomy and repeated cryoablations for pulmonary metastases were performed (repeat OMD). The patient is currently alive in very good condition without evidence of disease 4.5 years after the first diagnosis of OMD and free of systemic therapy. Clinical decision-making, local treatment options, and favorable biological tumor behavior in OMD are discussed. In this case of oligometastatic esophageal squamous cancer with favorable biological behavior, sequential local treatment of OMD (i.e. metastasectomy and cryoablations) combined with primary tumor resection was associated with long-term OS. • Oligometastatic disease (OMD) is associated with favorable tumor biology. • Local treatment for OMD may improve overall survival (OS). • Treatment for OMD is highly complex and requires a multidisciplinary team.

Resection of metastases in patients with BRAF mutated metastatic colon cancer: results of a multicenter retrospective study

Introduction: local treatment of metastases is an integral part of colon cancer treatment. However, there is not enough data on the efficacy of surgical resection of metastases in patients with a BRAF gene mutation to recom‑mend this approach in routine practice. We initiated a retrospective multicenter study to assess the incidence of BRAF gene mutations in patients with metastatic colon cancer and to study the efficacy of metastasectomy in this group of patients.Materials and methods: we selected all patients who underwent surgical resection of metastases in various sites from the database of patients with BRAF gene mutations created as a result of a multicenter retrospective study with participation of 7 clinics in the Russian Federation. All 57 patients with RAS gene mutations and 43 patients with wild‑type RAS and BRAF genes who also underwent surgical resection of metastases at any stage of treatment were selected from the register of the Chemotherapy Department No. 2 of the NMRC of Oncology named after N. N. Blokhin for comparative analysis. Disease‑free survival and overall survival were used as primary efficacy criteria.Results: we found 26 patients with BRAF gene mutations who underwent surgical resection of metastases. When comparing disease‑free survival, the worst median was achieved in the group of patients with BRAF gene mutations: 7 months versus 14 months in patients with RAS gene mutations (HR 0.4, 94 % CI 0.23–0.7, P = 0.006); median disease‑free survival was not achieved in the wild‑type RAS and BRAF group (HR 0.2, 95 % CI 0.11–0.45, P &lt;0.001).The median overall survival in the BRAF gene mutation group was 26 months versus 38 months in the RAS gene mutations group (HR 0.8, 95 % CI 0.33–1.98, P = 0.6) and 49 months in the wtRAS/wtBRAF group (RR 0.46, 95 % CI 0.17–1.24, P = 0.1). Resection of recurrent tumors in patients with metastases in retroperitoneal lymph nodes was associated with extremely low disease‑free survival (2 months); at the same time, disease‑free survival was 7 months after resection of isolated metastases in the liver and 8 months for metastases in the peritoneum.Conclusion: prognosis of patients with a BRAF gene mutation after surgical resection of metastases is worse than in patients with a different mutation phenotype. Nevertheless, literature data, as well as the results of our study, confirm the possibility of performing metastasectomy with careful selection of patients.

Néoplasies neuro-endocrines broncho-pulmonaires primitives : tumeurs carcinoïdes et carcinomes neuro-endocrines à grandes cellules: Primary pulmonary neuroendocrine neoplasms : carcinoid tumors and large-cell neuro-endocrine carcinomas

Primary pulmonary neuroendocrine neoplasms comprise several distinct clinical entities, corresponding to four main subtypes: well differentiated neuroendocrine tumors including typical carcinoid tumors, of low grade malignancy and atypical carcinoids of intermediate grade; neuro-endocrine carcinomas with either small or large cells, which are high grade, frequent malignancy.The pre-treatment workup of carcinoid tumors is based on specific recommendations. Any clinical suspicion of an associated functional syndrome must be confirmed by the appropriate blood dosages.In case of metastatic carcinoid tumor, management relies on the control of a possible secretory syndrome, in addition to the oncological treatment, based on the evaluation of tumor progression, with several opportunities: close follow-up, local treatment of metastases, treatment with somatostatin analogues, everolimus, or chemotherapy for tumor with high aggressiveness. Peptide receptor radionuclide therapy with 177Lu-DOTATATE in patients with somatostatin receptor-expressing neuroendocrine tumors is an interesting option not yet validated for routine use.In case of advanced, metastatic large-cell neuroendocrine carcinoma, platinum and etoposide combination is generally used in front line. No established second line is available. Results of the IFCT-FFCD-GERCOR “NIPINEC trial” evaluating nivolumab, with or without ipilimumab in the second- and third-line setting are awaiting. Molecular analysis of a panel of oncogenic alterations could guide therapeutic decision.© 2021 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Local treatment of metastases plus systemic chemotherapy on overall survival of patients with metastatic nasopharyngeal carcinoma.

BackgroundTo investigate the effect of local treatment of metastases on overall survival (OS) of patients with metastatic nasopharyngeal carcinoma (NPC).MethodsOne hundred and forty‐seven patients were included. The association between local treatment and OS was examined with propensity score matching (PSM) method.ResultsIn entire cohort, the median OS was significantly longer in patients with local treatment of metastases plus chemotherapy compared to those with chemotherapy alone (71.7 vs. 16.2 months; p < 0.001). In PSM cohort, similar OS benefit of patients with local treatment was observed (55.6 vs. 17.6 months; p = 0.011). The survival benefit of local treatment remained regardless of the number of metastatic lesions and metastatic sites. Patients received radiation doses of >60 Gy had longer OS than those who received less.ConclusionsLocal treatment of metastases could improve OS of patients with metastatic NPC and could be considered in their treatment in addition to chemotherapy.

PCN78 Costs of Recurrence in Patients with HER2+ Breast Cancer in Spain

Previous studies estimated the cost of recurrences in HER2+ breast cancer (BC) patients in Spain. Considering the advances in the management of the disease, the aim of this study is to update and describe the costs of recurrences in patients with HER2+ BC in Spain. The average cost of a HER2+ BC recurrence was estimated considering direct and indirect costs of local and metastatic relapses (up to 5 lines in the metastatic setting) weighted by the proportion of patients reaching each treatment line according to published literature and validated by an expert panel. Unit costs were obtained from literature and national databases and were updated to €2020. Direct cost estimates included pharmacological treatments and other medical resources (visits, tests, hospitalizations, local treatments [surgery and radiotherapy], adverse events management and treatment of localized metastases) and were validated by an expert panel. Indirect costs were estimated using the human capital approach. In local relapses, direct costs were €36,367 whereas indirect costs were €20,210. In metastatic relapses, direct costs ranged between €124,657 (patients receiving one treatment line) and €243,853 (patients receiving five treatment lines), and indirect costs ranged between €14,510 and €44,525, respectively. The average cost of the recurrence per patient weighting both local and metastatic relapses was €196,078 (86% direct costs, of which 84% were pharmacological treatments and 16% other medical resources). The average cost of the recurrence per patient weighting only metastatic relapses was €204,753 (87% direct costs, of which 85% were pharmacological treatments). HER2+ BC recurrences continue posing a high economic burden on the Spanish National Healthcare System and the society. Tackling the disease at an early stage reducing the risk of recurrences remains a paramount priority in the management of the disease.

Tumeurs neuro-endocrines broncho-pulmonaires primitives : tumeurs carcinoïdes et carcinomes neuro-endocrines à grandes cellules: Primary pulmonary neuroendocrine tumors: Carcinoid tumors and large-cell neuro-endocrine carcinomas

AbstractPrimary pulmonary neuroendocrine tumors comprise several distinct clinical entities, corresponding to four main subtypes: typical carcinoid tumors, of low grade malignancy; atypical carcinoids of intermediate grade; neuro-endocrine carcinomas with either small or large cells, which are high grade, frequent malignancy.The pre-treatment workup of carcinoid tumors is based on specific recommendations. Any clinical suspicion of an associated functional syndrome must be confirmed by the appropriate blood dosages.In case of metastatic carcinoid tumor, management relies on the control of a possible secretory syndrome by somatostatin analogues, in addition to the oncological treatment, based on the evaluation of tumor progression, with several opportunities: close follow-up, local treatment of metastases, treatment with somatostatin analogues, everolimus, or chemotherapy for tumor with high aggressiveness.In case of advanced, metastatic large-cell neuroendocrine carcinoma, molecular analysis of a panel of oncogenic alterations could guide the chemotherapy strategy; platinum and etoposide combination has historically been used. In the second line, in the absence of any therapeutic standard, the IFCT-FFCD-GERCOR “NIPINEC trial” is recruiting in France in and aims at evaluating nivolumab, with or without ipilimumab in the second- and third-line setting.© 2020 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Circulating tumor DNA as a marker of minimal residual disease following local treatment of metastases from colorectal cancer

Background Local treatment of liver and/or lung metastases from colorectal cancer (CRC) is increasingly used in daily practice and comprises resection, radiofrequency ablation (RFA) and stereotactic radiotherapy (SBRT). The need for prognostic markers for patients undergoing such treatment is currently unmet. We investigated post-treatment circulating tumor-specific DNA (ctDNA) analysis and address a possible prognostic value in a pilot study. Materials From July 2015 to September 2017, patients undergoing standard of care local treatment of liver and/or lung metastases were included in a prospective translational study. Blood samples were drawn 2 weeks after local treatment and during follow-up. CtDNA was detected by ddPCR and a mass spectrometry-based platform MassARRAY®. Results Post treatment blood samples were available for 35 patients including five with detectable ctDNA (KRAS mutation, n = 2; NRAS mutation, n = 2; BRAF mutation, n = 1) by ddPCR. 17 out of 35 patients (49%) developed recurrence within a median of 273 days (95%CI 95–NA) among patients positive for ctDNA, while the median time to recurrence was not reached for the group of patients negative for ctDNA (p = .03). Conclusion The presence of ctDNA following local treatment of metastatic CRC is associated with an increased risk of recurrence and a short time to failure.

Safety and Feasibility of Additional Tumor Debulking to First-Line Palliative Combination Chemotherapy for Patients with Multiorgan Metastatic Colorectal Cancer.

IntroductionLocal treatment of metastases is frequently performed in patients with multiorgan metastatic colorectal carcinoma (mCRC) analogous to selected patients with oligometastatic disease for whom this is standard of care. The ORCHESTRA trial (NCT01792934) was designed to prospectively evaluate overall survival benefit from tumor debulking in addition to chemotherapy in patients with multiorgan mCRC. Here, we report the preplanned safety and feasibility evaluation after inclusion of the first 100 patients.MethodsPatients were eligible if at least 80% tumor debulking was deemed feasible by resection, radiotherapy and/or thermal ablative therapy. In case of clinical benefit after three or four cycles of respectively 5‐fluorouracil/leucovorin or capecitabine and oxaliplatin ± bevacizumab patients were randomized to tumor debulking followed by chemotherapy in the intervention arm, or standard treatment with chemotherapy.ResultsTwelve patients dropped out prior to randomization for various reasons. Eighty‐eight patients were randomized to the standard (n = 43) or intervention arm (n = 45). No patients withdrew after randomization. Debulking was performed in 82% (n = 37). Two patients had no lesions left to treat, five had progressive disease, and one patient died prior to local treatment. In 15 patients (40%) 21 serious adverse events related to debulking were reported. Postoperative mortality was 2.7% (n = 1). After debulking chemotherapy was resumed in 89% of patients.ConclusionTumor debulking is feasible and does not prohibit administration of palliative chemotherapy in the majority of patients with multiorgan mCRC, despite the occurrence of serious adverse events related to local treatment.Implications for PracticeThis first prospective randomized trial on tumor debulking in addition to chemotherapy shows that local treatment of metastases is feasible in patients with multiorgan metastatic colorectal cancer and does not prohibit administration of palliative systemic therapy, despite the occurrence of serious adverse events related to local treatment. The trial continues accrual, and overall survival (OS) data and quality of life assessment are collected to determine whether the primary aim of >6 months OS benefit with preserved quality of life will be met. This will support evidence‐based decision making in multidisciplinary colorectal cancer care and can be readily implemented in daily practice.

Metastatic colorectal cancer prior to expanded RAS assessment: evidence from long-term outcome analysis of a real-life cohort within a dedicated colorectal cancer unit

BackgroundMolecular assessment and treatment of metastatic colorectal cancer (mCRC) quickly evolved during the last decades, hampering longitudinal evaluation of prognostic markers. The aim of this study was to evaluate prognostic predictors of long-term survival in a retrospective series of mCRC, treated prior to the expanded RAS assessment era.MethodsmCRC cases treated at the Città della Salute e della Scienza University Hospital (Turin, Italy) between January 2004 and December 2012 were evaluated, including cases with ≥ 5-year follow-up only. Long-term survival was defined as an overall survival (OS) ≥ 4 years based on the observed OS interquartile range values. Univariate/multivariate Cox proportional hazards regression models were performed to assess the prognostic significance of the clinical/biological features, while binary logistic regression models were used to verify their associations with long-term survival.ResultsTwo hundred and forty-eight mCRC cases were included and analyzed. Sixty out of two hundred and forty-eight (24%) patients were long-term survivors. Univariate binary logistic regression analysis demonstrated a significant association between long-term survival and age at diagnosis < 65 (OR = 2.28, p = 0.007), single metastatic site (OR = 1.89, p = 0.039), surgical resection of metastases (OR = 5.30, p < 0.001), local non-surgical treatment of metastases (OR = 4.74, p < 0.001), and a bevacizumab-including first-line treatment schedule (OR = 2.19, p = 0.024). Multivariate binary logistic regression analysis confirmed the prognostic significance of surgical resection of metastases (OR = 3.96, p < 0.001), local non-surgical treatment of metastases (OR = 3.32, p = 0.001), and of bevacizumab-including first-line treatment schedule (OR = 2.49, p = 0.024).ConclusionLong-term survival could be achieved in a significant rate of patients with mCRC even in an era of limited molecular characterization. Local treatment of metastases proved to be a significant predictor of long-term survival.

Clinical outcomes of patients with duodenal adenocarcinoma and intestinal-type papilla of Vater adenocarcinoma.

BACKGROUNDDuodenal adenocarcinoma (DA) and intestinal-type papilla of Vater adenocarcinoma (it-PVA) are rare malignancies of the gastrointestinal tract. Current therapeutic options are translated nowadays from treatment strategies for patients with colorectal cancer due to histopathological similarities.AIMTo retrospectively investigate the clinical outcome of patients with DA and it-PVA.METHODSAll patients with DA and it-PVA diagnosed between 2000 and 2017 were included at two academic centers in the Netherlands. All patients with histopathologically-confirmed DA or it-PVA were eligible for inclusion. Clinical outcome was compared between DA and it-PVA per disease stage. In the subgroup of stage IV disease, survival after local treatment of oligometastases was compared with systemic therapy or supportive care.RESULTSIn total, 155 patients with DA and it-PVA were included. Patients with it-PVA more often presented with stage I disease, while DA was more often diagnosed at stage IV (P < 0.001). Of all patients, 79% were treated with curative intent. The median survival was 39 mo, and no difference in survival was found for patients with DA and it-PVA after stratification for disease stage. Seven (23%) of 31 patients with synchronous stage IV disease underwent resection of the primary tumor, combined with local treatment of oligometastases. Local treatment of metastases was associated with an overall survival of 37 mo, compared to 14 and 6 mo for systemic therapy and supportive care, respectively.CONCLUSIONSurvival of patients with DA and it-PVA is comparable per disease stage. These results suggest a potential benefit for local treatment strategies in selected patients with oligometastases, although additional prospective studies are needed.

669TiP - The ORCHESTRA trial; A phase III trial of adding tumour debulking to systemic therapy versus systemic therapy alone in multi-organ metastatic colorectal cancer (mCRC)

BackgroundFor selected patients with oligometastatic colorectal cancer (mCRC), local treatment of metastases is standard of care based on retrospective reports showing long term survival rates. Local treatment of metastases is technically feasible in an increasing number of patients with multi-organ mCRC. It is unknown whether patients with extensive disease will benefit from tumor debulking when added to first line palliative chemotherapy.The aim of the ORCHESTRA trial (NCT01792934) is to improve overall survival (OS) with at least six months by maximal tumor debulking in combination with systemic therapy in patients with multi-organ mCRC. Trial designPatients with multi-organ mCRC are eligible if≥80% tumor debulking is deemed feasible by resection, radiotherapy and/or thermal ablative therapy. All patients receive 5FU and oxaliplatin based chemotherapy ± bevacizumab. In case of response or stable disease at first evaluation (+/- 2 months), patients are randomized to continuation of chemotherapy or maximal tumor debulking followed by continuation of chemotherapy. A total of 478 patients will be included to meet the primary endpoint (≥ 6 months OS benefit, power 80%, 5% type I error rate two sided). We define local treatments feasible when they can be performed within a 3-month time period to prevent extensive delay of systemic therapy. Quality of life is an important secondary endpoint of the trial. Tissue and blood specimen are collected for translational research. Currently, 290 patients are included in 27 participating Dutch hospitals. Several centers in the United Kingdom will soon participate in the trial. Clinical trial identificationNCT01792934. Legal entity responsible for the studyAmsterdam University Medical Center, Location VUmc. FundingThe ORCHESTRA trial is financially supported by KWF (Dutch Cancer Foundation), Blokker-Verwer foundation and Roche. DisclosureAll authors have declared no conflicts of interest.

Tumeurs neuro-endocrines broncho-pulmonaires primitives: tumeurs carcinoïdes et carcinomes neuro-endocrines à grandes cellules

Primary pulmonary neuroendocrine tumors comprise several distinct clinical entities, corresponding to four main subtypes: typical carcinoid tumors, of low grade malignancy; atypical carcinoids of intermediate grade; neuro-endocrine carcinomas with either small or large cells, which are high grade, frequent malignancy.The pre-treatment workup of carcinoid tumors is based on specific recommendations. Any clinical suspicion of an associated functional syndrome must be confirmed by the appropriate blood dosages.In case of metastatic carcinoid tumor, management relies on the control of a possible secretory syndrome by somatostatin analogues, in addition to the oncological treatment, based on the evaluation of tumor progression, with several opportunities: close follow-up, local treatment of metastases, treatment with somatostatin analogues, everolimus, or chemotherapy for tumor with high aggressiveness.In case of advanced, metastatic large-cell neuroendocrine carcinoma, molecular analysis of a panel of oncogenic alterations could guide the chemotherapy strategy; platinum and etoposide combination has historically been used. In the second line, in the absence of any therapeutic standard, the IFCT-FFCD-GERCOR “NIPINEC trial” is recruiting in France in and aims at evaluating nivolumab, with or without ipilimumab in the second- and third-line setting.

Tumeurs neuro-endocrines broncho-pulmonaires primitives : tumeurs carcinoïdes, carcinomes neuro-endocrines à grandes cellules

Primary pulmonary neuroendocrine tumors comprise several distinct clinical entities, corresponding to four main subtypes : typical carcinoid tumors, of low grade malignancy ; atypical carcinoids of intermediate grade ; neuro-endocrine carcinomas with either small or large cells, which are high grade, frequent malignancy.The pre-treatment workup of carcinoid tumors is based on specific recommendations. Any clinical suspicion of an associated functional syndrome must be confirmed by the appropriate blood dosages.In case of metastatic carcinoid tumor, management relies on the control of a possible secretory syndrome by somatostatin analogues, in addition to the oncological treatment, based on the evaluation of tumor progression, with several opportunities : close follow-up, local treatment of metastases, treatment with somatostatin analogues, everolimus, or chemotherapy for tumor with high aggressiveness.In case of advanced, metastatic large-cell neuroendocrine carcinoma, molecular analysis of a panel of oncogenic alterations could guide the chemotherapy strategy ; platinum and etoposide combination has historically been used. In the second line, in the absence of any therapeutic standard, the IFCT-FFCD-GERCOR NIPINEC trial is opening in France in 2018 and aims at evaluating nivolumab, with or without ipilimumab in the second- and third-line setting.

The value of tumour debulking for patients with extensive multi-organ metastatic colorectal cancer

Local treatment of metastases by surgical resection or other ablative therapies is technically feasible in an increasing number of patients with multi-organ metastatic cancer. This results in a growing debate on whether patients with extensive disease, that is traditionally deemed unresectable, may benefit from local treatment of metastases when added to standard palliative systemic therapy. For selected patients with oligometastatic colorectal cancer, local treatment of metastases has become the standard of care based on retrospective reports showing long-term survival rates. In addition to systemic therapy, preliminary evidence suggests that patients with extensive metastatic colorectal cancer may also benefit from local treatment. Here, we present the future perspectives based on the available literature on local treatment approaches in colorectal cancer.

The impact of [68Ga]PSMA I&T PET/CT on radiotherapy planning in patients with prostate cancer.

To determine the impact of Gallium-68-labled prostate-specific membrane antigen positron-emission tomography/computed tomography ([68Ga]PSMA PET/CT) on radiotherapy planning for primary disease, biochemical cancer relapse, and advanced disease of prostate cancer. Atotal of 106 patients with prostate cancer scheduled for radiation therapy underwent 120[68Ga]PSMA PET/CT scans prior to radiotherapy treatment. In 20cases, patients underwent [68Ga]PSMA PET/CT for primary therapy(PT), 75cases were referred for biochemical relapse after surgery(RL), and 25cases were intended for palliative treatment of localized metastases(MD). We retrospectively compared the impact of [68Ga]PSMA PET/CT on lesion detection and treatment decision to CT alone. [68Ga]PSMA PET/CT revealed atotal of 271 positive lesions, whereas CT detected 86lesions (32%). Overall, the radiotherapy regime was changed in 55 of 120 cases (46%) based on the higher detection rate of [68Ga]PSMA PET/CT: in 15% of cases with PT, in 43% of cases with RL, and in 44% of cases with MD. [68Ga]PSMA PET/CT is superior to CT alone for lesion detection in prostate cancer, thereby significantly impacting on radiotherapy planning for primary disease, biochemical cancer relapse, and advanced disease of prostate cancer.