Surgical Management and Reconstruction of Diaphragm, Pericardium and Chest Wall in Mesothelioma Surgery: A Review

Mesothelioma is an aggressive disease arising from parietal pleura. Surgery is a valuable option in the frame of a multimodality treatment. Several surgical approaches have been standardized with the aim of a macroscopic complete resection; these often require homolateral diaphragm and pericardial resection and reconstruction. Extrapleural pneumonectomy (EPP) and extended pleurectomy decortication (EPD) have been recognized as radical surgical procedures. Nevertheless, both operations are technically challenging and associated with a significant rate of peri-operative morbidity and non-negligible mortality. The diaphragmatic and pericardial reconstruction technique is mandatory to avoid respiratory impairment and to reduce post-operative complications like gastric and cardiac herniation. Moreover, in the case of localized chest wall recurrence, surgery might be considered a valuable therapeutical option for highly selected and fit patients. All the technical aspects of the resection and reconstruction of the diaphragm, pericardium, and chest wall are described as well as the possible use of new minimally invasive techniques. In addition, the choice of different prosthetic materials, considering the most recent innovations in the field, are discussed.

Multi-center randomized study of pembrolizumab/carboplatin versus carboplatin alone in patients with chest wall disease from breast cancer: TBCRC 044.

TPS1111 Background: Chest wall recurrence is a subtype of breast cancer that is challenging to treat, and associated with a short duration of response to treatment and an increased risk of development of distant metastases. Given the inflammatory nature of this disease and the association of chest wall disease with lymphovascular invasion, which is correlated with higher programmed cell death 1 (PD-1) expression, we hypothesized that immunotherapy may be beneficial as treatment. Combinations of immunotherapy and chemotherapy have a synergistic effect and demonstrated efficacy in the treatment of metastatic triple negative breast cancer (TNBC). This study is evaluating the efficacy of pembrolizumab, an anti-PD-1 antibody, in combination with carboplatin, in patients with chest wall infiltration from breast cancer. This drug combination has shown efficacy in advanced lung cancer. Methods: This is a multicenter, 2:1 randomized phase II study of pembrolizumab/carboplatin (Arm A, 56 patients) vs. carboplatin (Arm B, 28 patients) in 84 patients with chest wall disease from breast cancer, with or without distant metastases. Patients may have TNBC, hormone receptor positive/HER2 negative (following receipt of 2 prior hormone therapies), or HER2 positive breast cancer (with option to continue trastuzumab on study). Pembrolizumab is administered as 200 mg IV every 3 weeks, and carboplatin as AUC 5 IV every 3 weeks. Patients on Arm A may continue pembrolizumab +/- carboplatin (Arm Ax) after completion of 6 cycles of treatment, while patients in Arm B can cross-over to pembrolizumab (+/- carboplatin) on progression (Arm Bx). Patients must have adequate organ function, performance status ≤ 2, and may have received any number of lines of prior chemotherapy. Patients undergo serial chest wall photography and imaging (CT chest, abdomen, and pelvis, and bone scan) at baseline and every 6 weeks, as well as blood collection for correlative studies and chest wall biopsies at baseline and after 2 cycles of treatment. The primary endpoint is disease control rate (RECIST 1.1) at 18 weeks of treatment, and the study is powered to determine a 20% difference in disease control rates between arms (HR 0.52, a = 0.10, ß = 0.20). An interim analysis will occur for Arm B after 18 patients are enrolled, with a stopping rule for futility. Secondary endpoints include progression-free survival, toxicity (NCI CTCAE), and response based on irRECIST and tumor programmed death ligand 1 (PD-L1) expression. Exploratory objectives include evaluating changes in soluble PD-L1, tumor and peripheral blood immune composition, circulating tumor cells and cell-free DNA, and MYC oncogene expression. This study (NCT03095352) is open at 7 sites in the Translational Breast Cancer Research Consortium (TBCRC). 52 patients are enrolled. Grant funding is provided by Merck and UCSF. Clinical trial information: NCT03095352 .

The Prognostic Value of Skin Involvement in Breast Cancer Patients With Chest Wall Recurrence

Background: To assess the prognosis of skin involvement in female breast cancer patients with chest wall recurrence (CWR).Methods: We retrospectively analyzed the clinical-pathological data of breast cancer patients with CWR who were diagnosed pathologically between January 2000 and April 2020. Progression free survival (PFS) was defined as time from diagnosis of CWR to the first disease progression. Persistent chest wall progression was three consecutive chest wall progression without distant organ involvement.Results: A total of 476 patients with CWR were included in this study. Among them, skin involvement or not was queried and confirmed in 345 patients. Skin involvement was significantly correlated to tumor size (P=0.003) and initial nodal status (P<0.001). By Kaplan-Meier analysis, skin involvement predicted a shorter PFS (P<0.001), especially local disease progression (P<0.001). Skin involvement was an independent biomarker for PFS by the multivariate analysis (P=0.034). Patients with skin involvement were more likely to experience persistent chest wall progression (P=0.040). After eliminating the potential deviation caused by insufficient follow-up time, persistent chest wall progression was more likely to be associated with positive lymph nodal status (P=0.046), negative PR (P=0.001) and positive HER2 (P=0.046) of the primary site, negative ER (P=0.027) and PR (P=0.013) of chest wall lesion and skin involvement (P=0.020).Conclusion: Skin involvement predicted poor local disease control in female breast cancer patients with CWR and it was more likely to be related to persistent chest wall progression. We improved the stratification of prognosis and provided new insights for biological behaviors of the disease and further individualized treatment in breast cancer patients with CWR.

Cutaneous Metastasis vs. Isolated Skin Recurrence of Invasive Breast Carcinoma after Modified Radical Mastectomy

Background. Five to ten percent of the patients with operable breast cancer develop a chest wall recurrence within 10 years following the mastectomy. One of the most distressing presentations of locally recurrent breast cancer is the appearance of cutaneous metastases. To the best of authors’ knowledge, there is no study distinguishing skin metastasis from local recurrence, so the main aim of this report was to elucidate if these two features are important in the prognosis and management of the disease. Case Presentation. A 51-year-old woman referred to the breast clinic due to a painful mass in the left breast. The patient underwent the modified radical mastectomy (MRM) and left axillary lymph node dissection followed by 30 sessions of radiotherapy and 8 sessions of chemotherapy (T3N1M0, ER−, and HER2+). About 15 months after the surgery, she presented with redness and eruptive lesions over the mastectomy scar that increased in size within a three-month follow-up. Conclusion. Mastectomy is not an absolute cure in the treatment of an invasive breast cancer because almost always, there is a recurrence risk and possibility of metastasis. It is vital to differentiate between local recurrence and skin metastasis because it would alter the overall treatment decision, prognosis, and patient outcomes.

Prognosis and Prophylactic Regional Nodal Irradiation in Breast Cancer Patients With the First Isolated Chest Wall Recurrence After Mastectomy

Background and PurposeOptimal radiation target volumes for breast cancer patients with their first isolated chest wall recurrence (ICWR) after mastectomy are controversial. We aimed to analyze the regional failure patterns and to investigate the role of prophylactic regional nodal irradiation (RNI) for ICWR.Materials and MethodsAltogether 205 patients with ICWR after mastectomy were retrospectively analyzed. Post-recurrence progression-free survival (PFS) and overall survival (OS) rates were calculated by Kaplan-Meier method and the differences were compared with Log-rank test. Competing risk model was used to estimate the subsequent regional recurrence (sRR) and locoregional recurrence (sLRR) rates, and the differences were compared with Gray test.ResultsThe 5-year sRR rate was 25.2% with median follow-up of 88.6 months. Of the 52 patients with sRR, 30 (57.7%) recurred in the axilla, 29 (55.8%) in supraclavicular fossa (SC), and five (9.6%) in internal mammary nodes. Surgery plus radiotherapy was independently associated with better sLRR and PFS rates (p&lt;0.001). The ICWR interval of ≤ 4 years was associated with unfavorable sRR (p=0.062), sLRR (p=0.014), PFS (p=0.001), and OS (p=0.005). Among the 157 patients who received radiotherapy after ICWR, chest wall plus RNI significantly improved PFS (p=0.004) and OS (p=0.021) compared with chest wall irradiation alone. In the 166 patients whose ICWR interval was ≤ 4 years, chest wall plus RNI provided the best PFS (p&lt;0.001) and OS (p=0.022) compared with chest wall irradiation alone or no radiotherapy.ConclusionPatients with ICWR have a high-risk of sRR in SC and axilla. Chest wall plus RNI is recommended.