Background Immunotherapy is revolutionising the treatment of patients diagnosed with melanoma and other cancers. The first immune checkpoint inhibitor, ipilimumab (targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)), showed a survival advantage over standard chemotherapy. Subsequently the anti-programmed cell death protein 1 (PD-1) antibodies, nivolumab and pembrolizumab were shown to be more effective than ipilimumab. Ipilimumab combined with nivolumab gives an incremental gain in overall survival compared with nivolumab alone but increases the risk of severe, potentially life-threatening toxicities. In contrast to ipilimumab monotherapy, anti-PD-1 antibodies are licensed to be continued until disease progression. Follow-up of patients recruited to the first trials evaluating 2 years of pembrolizumab showed that three-quarters of responding patients continue responding after stopping treatment. Suggestive of early response, we hypothesised that continuing anti-PD-1 treatment beyond 1 year in progression-free patients may be unnecessary and so designed the DANTE trial. Methods DANTE is a multicentre, randomised, phase III, non-inferiority trial to evaluate the duration of anti-PD-1 therapy in patients with metastatic (unresectable stage III and stage IV) melanoma. It uses a two-stage recruitment strategy, registering patients before they complete 1 year of first-line anti-PD-1 +/− CTLA-4 therapy and randomising eligible patients who have received 12 months of treatment and are progression-free at 1 year. At randomisation, 1208 patients are assigned (1:1) to either 1) continue anti-PD-1 treatment until disease progression/ unacceptable toxicity/ for at least 2 years in the absence of disease progression/ unacceptable toxicity or 2) to stop treatment. Randomisation stratifies for baseline prognostic factors. The primary outcome is progression-free survival at 3, 6, 9 and 12 months and then, 6-monthly for up to 4-years. Secondary outcomes collected at all timepoints include overall survival, response-rate and duration and safety, with quality of life and cost-effectiveness outcomes collected 3-monthly for up to 18-months. Sub-studies include a qualitative analysis of patient acceptance of randomisation and sample collection to inform future translational studies into response/ toxicity biomarkers. Discussion DANTE is a unique prospective trial investigating the optimal duration of anti-PD-1 therapy in metastatic melanoma patients. Outcomes will inform future use of these high burden drugs. Trial registration ISRCTN15837212, 31 July 2018.
discharge (n ¼ 8), pain (n ¼ 10), tenesmus (n ¼ 3), and numbness (n ¼ 1). The median time interval of re-irradiation from original RT was 33 months (inter-quartile range ¼ 13-65 months). There was definite evidence of symptomatic improvement in more than 50% of patients (n ¼ 11) with only 3 patients reporting no improvement in local symptoms. Six patients were discharged following re-irradiation and had limited follow-up to comment on the level of symptomatic improvement. Most importantly, there were no reports of significant toxicity and only one patient reported grade 2 fatigue and nausea. The median survival of patients who had previously received RT for localised disease was 10.25 months (range¼7.3-13.1 months) after irradiation. Conclusion: Palliative re-irradiation with 15 Gy in 5 fractions is well tolerated in patients with rectal cancer and associated with good symptomatic improvement and minimal toxicity. It should be considered as a possible therapeutic option in those with symptomatic loco-regional recurrence after previous radiotherapy. Further studies should be designed to evaluate the dose-response characteristics of reirradiated tissues with the aim of defining an optimum dose-level that may be safely employed to treat such patients. P À 316 Is there any association of dose received by pelvic bone marrow in preoperative radiotherapy in rectal cancer with hematological Onkologii-Instytut im. M. Sklodowskiej Curie, Warsaw, Poland Introduction: Preoperative radio(chemo)therapy in rectal cancer may irreversibly damage pelvic bone marrow (PBM) and impair the tolerance of subsequent chemotherapy. The aim of the study was to assess the association between irradiated volume of PBM and the tolerance of subsequent FOLFOX-4 chemotherapy in rectal cancer. Methods: The target population was a retrospective cohort of consecutive patients with adenocarcinoma of rectum who received FOLFOX-4 as adjuvant or because of cancer relapse in our institution between 2011-2016. The PBM was automatically contoured and divided into iliac (IM), lumbosacral (LSM), and lower pelvic (LPM) marrow. We assessed mean dose, and percentage of volume receiving 10-90% (V10%-V90%) of the prescribed dose for PBM, IM, LSM, LPM. To evaluate the association between mean dose, V20% and V40% with !2 (TOX2) and ! grade 3 (TOX3) hematological toxicity, Chi-2 and T-test were used. Generalized linear model (GLM) was used to test an influence of dose-volumes distribution on TOX2 and TOX3.Results: 39 patients met eligibility criteria. 26 of them received preoperative 5x5 Gy, 7 of them underwent 5x5 Gy with consolidative 3 cycles of FOLFOX-4, 6 of them received 25x2 Gy with concomitant 5-FU/LV. No dependence of V20% and V40% of PBM and its areas on toxicity was found. We found no influence of dose-volume distribution on TOX2 and TOX3. Conclusion:No relationship between doses received by pelvic bone marrow in preoperative radio(chemo)therapy in rectal cancer and hematological tolerance of subsequent FOLFOX-4 chemotherapy was found.
Background: Breast metastasis from the lung malignancy is very rare. An incidence of 0.1% to 1.6%. The most commonly of primary malignant diseases that metastasize to the breast are lymphoid tissue malignancy, malignant hemopoietic disease, and malignant melanoma. Method: In our experience we have had only one case with breast cancer metastasis from primary lung cancer. A 56-year-old female exsmoker manifested a right breast mass and lymphonodi in the right axillar region. She was treated for primary lung cancer stage IIB before 4 months. Although she was treated for right spontaneous pneumothorax six years ago through right posterolateral thoracotomy, wedge bullectomy superior dexter, fruotazh and pleural drainage. After 3 years she was treated and for metastasectomy left lung and lateral chest wall resection cost 6/7. Result: The patient underwent right local mastectomy and right axillary dissection. After histological and immunohistochemical analyzes showed that breast mass was metastasis from a primary lung carcinoma Conclusion: Accuracy treatment and prognosis of the breast metastasis from primary lung cancer is differentiation from the primary breast cancer and is very important to do this differentiation.
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