Ablative Therapy of Oligometastatic Tumor After Response to Conventional First Line Treatment

Advancements in systemic antineoplastic therapies have led to improved overall survival rates for many solid tumors. However, metastatic disease remains a significant challenge and remains the leading cause of mortality for these patients. Additionally, there is a high attrition rate after first-line standard treatment across various tumor types, with studies indicating that 20-70% of patients may be unable to undergo second-line therapy, depending on the tumor type. This highlights an urgent need to enhance outcomes from the first line of treatment. Although first-line therapy often represents the best available option, most patients experience relapse and disease progression despite an initial tumor response. This is attributed to both intrinsic and acquired resistance arising from the heterogeneity of primary tumors and metastases. To address this issue, metastasis-directed therapy (MDT) has been explored as a way to reduce tumor burden and mitigate the risk of resistance due to therapeutic selective pressure. MDT offers a promising opportunity to improve first-line treatment outcomes, but more precise patient selection criteria are needed to maximize therapeutic benefit and minimize the potential toxicity of ablative therapies. Indeed, despites its efficacy, fatal complication may occur so do grade 3 to 4 toxicities. Toxicity depends of the local ablative therapy (LAT) planned but as it will never be none, oncologists have to propose invasive treatment to patient that may benefit the most. Based on the published data, the investigators propose a pragmatic, selective approach centered on sensitivity to systemic therapy. The investigators aim to evaluate the benefit of local ablative therapy (LAT) in patients who demonstrate non-progressive disease after three months of first-line standard of care. Given the importance of this question across cancer subtypes, the investigators will employ a prospective database to enroll patients with various solid tumor type, excluding the ones for which the impact of LAT has already been explored or may be difficult to achieve. Outcomes of this strategy will be evaluated compared to outcomes from pivotal studies defining optimal standard first line therapy (OST) . Several analyses will be performed to better characterize the population for whom a multimodal approach may significantly improve their survival. The first one will aim to compare the median duration of response (mDOR) of the population treated with LAT compared to the mDOR reported by the pivotal study(ies) of each OST. This study will serve as a proof of concept, supporting chemosensitivity as a viable selection factor for multimodal treatment in a broad range of cancer types. Primary objective: Improvement of the duration of response (DOR) after completion of LAT compared to DOR reported in pivotal study that evaluated first line OST. Secondary objectives: * Evaluation of the safety of the addition of LAT. * Evaluation of overall progression free survival (PFS) and PFS at 1 year. * Evaluation of overall survival from OST start and from the time of LAT completion. * Documentation of acceptance and compliance to LAT decision by the institutional expert committee

Sex

All

Minimum age

18 Years

Inclusion Criteria:

1. Performance status 0 or 1 on the Eastern Cooperative Oncology Group (ECOG).
2. Histologically diagnosis of one of these tumour types:

   1. Hormone receptor positive, HER2 negative breast cancer
   2. Triple negative breast cancer
   3. HER2+ breast cancer
   4. Non small cell lung cancer without oncogenic addiction
   5. Head and Neck squamous cell carcinoma without recurrence in the radiation field
   6. Gastric adenocarcinoma
   7. Esophageal cancer (adenocarcinoma or epidermoid carcinoma)
   8. Recurrent pancreatic cancer without local recurrence
   9. Anal cancer
   10. Bladder cancer
   11. Clear cells renal cell carcinoma
   12. Prostate cancer sensitive to castration
   13. Adenocarcinoma endometrial cancer
   14. Epidermoid carcinoma or adenocarcinoma of the cervix
   15. Colorectal cancer
   16. Recurrent Soft Tissue Sarcoma
   17. Melanoma
3. Patient with a decision by the local team to give OST and effective administration of OST. OST is defined as the most efficient choice in terms of survival in first line of advanced disease according to ESMO or other international guidelines. In case of multiple choice as first line, if no data provided direct evidence of superiority from one or the other options, there are all considered as OST. If the patient received a less efficient treatment because of his comorbidity or frailty, the eligible criteria won't be fulfilled.
4. Have non-progressive disease after 3 to 6 months of treatment, and less than 6 weeks before presentation to the multidisciplinary team

   1. Patients with complete response and no target lesion are excluded.
   2. Patients with bone metastasis with remaining bone condensation or scare from tumoral activity may be eligible depending on metabolic activity of the lesion or local multidisciplinary committee decision concerning the risk of residual disease.
5. After 3 to 6 months of treatment, and less than 6 weeks before start of LAT, patient must have an oligometastatic disease defined as all lesions (including primitive lesion) amenable to local ablative treatment according to local investigator team and respective local committee.

Exclusion Criteria:

1. Patients who already received systemic antitumoral treatment in the advanced setting (including chemotherapy, immunotherapy, targeted therapy, …)
2. Patients without OST administration
3. Patients that have progressing lesion at any time point before decision of LAT by the expert committee
4. Has a known recent history of other invasive tumour, excepted if local investigator may provide histologically data that all active lesions targeted are from the same cancer primitive.
5. Radiotherapy or other LAT to any metastatic site before the start of OST.
6. Exclusion criteria specific for France: Vulnerable persons according to the article L.1121-6 of the public health law (CSP), adults who are the subject of a measure of legal protection or unable to express their consent according to article L.1121-8 of the CSP