High grade neuroendocrine carcinoma of the breast, first line and maintenance immunotherapy.

Small cell carcinomas (SCCs) are poorly differentiated neuroendocrine tumors that arise predominantly in the lung and gastrointestinal tract (GIT). Neuroendocrine carcinomas can occur in a variety of extrapulmonary sites throughout the body, including breast, larynx, GIT, prostate, urinary bladder, ovary and cervix. This is a case report of a 55-year-old Asian female patient with metastatic high-grade neuroendocrine carcinoma of unknown origin that responded notably to off-label nivolumab maintenance treatment after first-line carboplatin - etoposide chemotherapy and radiation. After 2 years of nivolumab after platinum-based chemotherapy results from PET-CT showed no residual disease and we proceeded to mastectomy.

Can thromboprophylaxis build a link for cancer patients undergoing surgical and/or chemotherapy treatment? The MeTHOS cohort study.

BACKGROUND: Patients with active cancer have a 4-sevenfold increased risk for venous thromboembolism (VTE) especially during systematic anticancer treatment. Simultaneously, surgery is an additional risk factor. METHODS: The Metaxas's Hospital THromboprophylaxis program in Oncological & Surgical Patients (MeTHOS) is a prospective, phase IV, observational, non-interventional cohort study, aiming to record the thromboprophylaxis practice patterns in high-risk active cancer patients undergoing surgical and/or chemotherapy treatment. RESULTS: We are reporting results from 291 ambulatory patients (median age: 67 years, Q1-Q3: 59-73 years, 54.6% males) who received anti-neoplastic treatment and administered thromboprophylaxis. 59.8% had cardiovascular disease (mostly hypertension), 76.6% were reported as having at least one comorbidity, while 27.5% and 15.8% accumulated two and three comorbidities, respectively. 94.9% of the patients were receiving highly thrombogenic agents such as platinum-based agents, 5-FU, immunotherapy, antiangiogenics/anti-VEGF, or erythropoietin. 26.5% of the patients were initially surgically treated. In terms of anticoagulation, all patients were treated with tinzaparin (fixed dose, 10,000 Anti-Xa IU, OD). The median anticoagulation duration was 6.2 months. Six thrombotic events were observed (2.06%, 95% CI: 0.76-4.43%): 5 were DVT, and one PE. With respect to safety, 7 bleeding events occurred (2.6%, 95% CI: 1.0-5.3%); 6 of them were minor. CONCLUSIONS: Thromboprophylaxis with LMWH in patients with active cancer and high thrombotic burden was safe and effective. Intermediate dose of tinzaparin seems to be an appropriate agent for cancer-associated thromboprophylaxis management. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT04248348.

Myeloablative chemotherapy and autologous stem cell transplantation can lead to successful postengraftment mobilization of hematopoietic progenitors to support planned subsequent cycle(s) of high-dose chemotherapy and autografting in a patient with relapsed germ-cell tumor.

Salvage high-dose chemotherapy (HDC) together with autologous hematopoietic stem cell (HSC) transplantation (ASCT) represents a curative treatment option for patients with relapsed/refractory germ-cell tumor. Usually, 2-3 cycles of HDC are administered with encouraging results, and a sizeable percentage of patients experience long-term survival. However, an appreciable number of patients fail to mobilize adequate numbers of HSCs, adequate to support more than one HDC cycle. There have been no data so far on remobilization of HSCs after prior autografting. We report a unique case with relapsed germ-cell tumor that had undergone the first cycle of HDC with myeloablative doses of carboplatin-etoposide, and HSCs were mobilized successfully in the early posthematopoietic engraftment period to support further cycles of HDC. Four weeks after the first ASCT, an identical second cycle of myeloablative HDC was administered and rescued successfully with the HSCs collected after engraftment following the previous HDC cycle. The present case report illustrates that HSCs can be mobilized successfully in the early postengraftment period after myeloablative doses of carboplatin-etoposide, and these cells can be applied as the sole source of hematopoietic rescue in planned sequential cycles of myeloablative HDC, leading to successful multilineage engraftment. Provided that more extensive experience is gathered in future studies in large numbers of patients, this strategy could prove helpful in patients who cannot initially collect sufficient HSC numbers, before the first autografting cycle, and are in need of sequential HDC+ASCT cycles. A detailed literature review is provided to highlight the uniqueness of the presented case.

Clinical history of patients with peritoneal carcinomatosis exluded from cytoreductive surgery & HIPEC.

PURPOSE: The aim of this study was to explore the natural course of peritoneal carcinomatosis (PC) in patients who are not fit to undergo cytoreductive (CRS) surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: Over an 8-year period (2006-2013) 320 patients were excluded from CRS and HIPEC at our center. Exclusion criteria were: (a) age >75 years; (b) ASA score ≥ 3; (c) extraperitoneal disease; (d) massive disease involvement of the small bowel; (e) disease involvement of the hepatic pedicle or the pancreas; (f) invasion of retroperitoneal space; (g) more than two stenoses of the small bowel. Another 130 patients underwent CRS and HIPEC. RESULTS: In the HIPEC group (N=130), the mean overall survival was 26.2±11.7 months, while from the non- HIPEC group (N=320), 200 patients underwent palliative surgery, with a mean overall survival of 11.7±8.3 months. Only 120 patients received palliative chemotherapy with a mean overall survival of 7.2±4.3 months. CONCLUSION: Our study suggests that, in patients unfit to undergo CRS & HIPEC, an exploratory laparotomy and palliative surgery should be performed, offering a survival benefit and improved quality of life.

Mapping the location of peritoneal metastases using the peritoneal cancer index and the correlation with overall survival: a retrospective study.

PURPOSE: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising treatment for patients with peritoneal carcinomatosis (PC). Our objective was to identify new prognostic factors within the Peritoneal Cancer Index (PCI) score in PC patients. METHODS: 140 patients (60 ovarian, 45 colon, 14 gastric, 10 pseudomyxoma peritonei, 5 mesothelioma, 6 sarcoma) with PC treated with CRS+HIPEC from 2007 to December 2013 were retrospectively included. Tumor extent and location were assessed by the PCI and residual disease was recorded using the Completeness of Cytoreduction (CC) score. All clinical data were computed in univariate and multivariate analysis using survival as primary endpoint. RESULTS: The PCI remains the most important factor concerning the long-term survival. Involved areas 4, 5 and 8 are more favorable in survival vs areas 9, 10 and 11, which predict a significantly worse outcome (p<0.002). Prognosis varies not only depending on how many peritoneal areas are involved but also on the location of the primary tumor. CONCLUSION: We demonstrated that the involvement of different areas in the PCI system has a significant impact on the final prognosis and survival.

Validation of Patras Immunotherapy Score model for prediction and prognosis of patients with advanced NSCLC treated with nivolumab or pembrolizumab: results from a European multicentre study.

Background: Recently, the Patras Immunotherapy Score (PIOS) has been developed to estimate the survival benefit of patients with advanced non-small-cell lung cancer (aNSCLC) treated with nivolumab or pembrolizumab. The aim of this study was to validate the clinical value of PIOS in an external cohort of aNSCLC patients. Methods: PIOS is a baseline formula produced by the combination of performance status, body mass index, age and line of treatment. In this multicentre study, 626 patients with confirmed NSCLC pathology, who had been treated with nivolumab or pembrolizumab, as well as 444 patients with aNSCLC, who had been managed with chemotherapy alone, were retrospectively enrolled. Predictive and prognostic values of PIOS were finally evaluated. Results: Patients treated with immunotherapy and higher PIOS score had an improved progression-free survival not only in univariate [hazard ratio (HR) = 0.621, p = 0.001], but also in multivariable analysis (HR = 0.651, p = 0.003). In addition, improved overall survival with increasing PIOS score was also observed (HR = 0.608, p < 0.001) with this association remaining statistically significant after adjusting for programmed-cell death ligand 1 (PD-L1) expression (HR = 0.620, p < 0.001). In addition, patients with disease progression (PD) had lower scores compared to those with stable disease (SD), partial response (PR) or complete response (CR) in a two-tier model (p < 0.001) as well as in a four-tier model (PD, SD, PR and CR; p < 0.001). Prognostic significance of PIOS score also persisted using a binary logistic regression analysis, adjusted for disease stage and PD-L1 status (p = 0.002, odds ratio: 0.578). Contrarily, PIOS had no prognostic significance in the chemotherapy group; however, upon combined analysis of the two cohorts, PIOS was found to have a significant interaction with the type of treatment (HR = 0.066 with p < 0.001), confirming its predictive value for immunotherapy. Conclusions: This study provides further validation of PIOS in aNSCLC patients treated with anti-PD-1 monotherapy.

Case Report: Combination of Olaparib With Chemotherapy in a Patient With ATM-Deficient Colorectal Cancer.

Poly-ADP ribose polymerase (PARP) inhibitors are constantly increasing in their indications for use as anti-cancer treatment in various neoplasms, the majority of which are linked with BRCA deficiency. Preclinical data support the investigation of PARP inhibitors in other neoplasms exhibiting "BRCAness" or homologous recombination deficiency (HRD) as monotherapy as well as in combination with chemotherapy. With the current report we present the case of a heavily pretreated 55-year-old male patient diagnosed with stage IV ATM-deficient CRC, who was effectively treated with an off-label olaparib-irinotecan combination after exhaustion of all available treatment choices; furthermore, we discuss the existing data providing evidence for the use of PARP inhibitors in ATM-deficient CRC and encourage the implementation of next-generation sequencing (NGS) in patients with no other available treatment options.

Plerixafor-aided Mobilization of Peripheral Blood Hematopoietic Stem Cells to Support Subsequent High-dose Chemotherapy After a Prior Autologous Transplant.

BACKGROUND: An appreciable proportion of patients in need of salvage high-dose chemotherapy (HDC) and autologous peripheral blood stem cell (PBSC) transplantation (PBSCT) fail to mobilize adequate numbers of hematopoietic progenitors, and plerixafor is applied for that purpose. Limited data exist on remobilization of PBSCs in patients who have relapsed after prior HDC + PBSCT. Herein, we report on consecutive patients that had undergone successful prior single or tandem HDC for a variety of malignant neoplasms in our institution, and later required re-mobilization of PBSCs in order to support further HDC cycles. PATIENTS AND METHODS: Plerixafor was administered in combination with granulocyte-colony stimulating factor alone, or after mobilizing chemotherapy. Five patients, 2 B-cell non-Hodgkin lymphomas, 1 multiple myeloma, 1 germ-cell tumor, and 1 Ewing sarcoma, having relapsed after prior HDC + PBSCT, were deemed candidates for further cycle(s) of PBSC-supported HDC. Plerixafor was applied in a "just-in-time" strategy after low CD34+ numbers were measured on the first day of anticipated hematopoietic stem cell collection (non-Hodgkin lymphoma, germ-cell tumor, and Ewing sarcoma), or pre-emptively in multiple myeloma. RESULTS: Successful collection of adequate PBSCs was achieved in all patients, from 1.8 to 3.8 × 106/kg after a median of 2 (range, 1-3) leukaphereses; 4 of 5 patients underwent subsequent HDC + PBSCT and engrafted after a median of 11 days (range, 9-55 days) and 25 days (range, 17-76 days) for neutrophils and platelets, respectively. CONCLUSION: Plerixafor proved effective to mobilize adequate numbers of PBSCs in individual patients with relapsed malignancies after prior single or tandem HDC + PBSCT. These PBSCs could establish sustained multi-lineage hematopoietic engraftment without any sequelae.

Trastuzumab combined with pegylated liposomal doxorubicin in patients with metastatic breast cancer. phase II Study of the Hellenic Cooperative Oncology Group (HeCOG) with biomarker evaluation.

OBJECTIVE: Combination of trastuzumab and anthracyclines in metastatic breast cancer (MBC) is precluded due to cardiotoxicity. Pegylated liposomal doxorubicin (PLD) is the least cardiotoxic among the anthracyclines. We performed a phase II study of trastuzumab and PLD with biomarker evaluation. METHODS: Patients with MBC and HER2 overexpression, assessed as 3+ at local laboratories, received trastuzumab 8 mg/kg as loading dose followed by 6 mg/kg in combination with PLD 30 mg/m(2), both given every 3 weeks. To be eligible, patients should have received first-line chemotherapy for MBC or should have relapsed within a year of adjuvant taxane. Tumor tissue blocks were collected for central review and exploratory biomarker evaluation. Left-ventricular ejection fraction (LVEF) was closely monitored by cardiac ultrasound. RESULTS: Among 37 patients, an overall response rate of 22% was observed with a progression-free survival (PFS) of 6.5 months (0.8-31.1, 95% CI 2.7-10.3) and a survival of 18.7 months (1.6-40.8, 95% CI 3.7-33.7). No decline in LVEF was noticed. Overexpression of mTOR and TOP2A gene alterations were associated with better PFS. PTEN gene deletion was associated with resistance to treatment. CONCLUSION: Trastuzumab combined with PLD every 3 weeks is feasible, effective and safe in HER2-positive patients.

Pegfilgrastim administered on the same day with dose-dense adjuvant chemotherapy for breast cancer is associated with a higher incidence of febrile neutropenia as compared to conventional growth factor support: matched case-control study of the Hellenic Cooperative Oncology Group.

OBJECTIVE: Recombinant human granulocyte-colony-stimulating factors such as filgrastim and pegfilgrastim have been employed as primary and secondary prophylaxis against neutropenia in cancer patients receiving chemotherapy. This study was conducted to evaluate the rate of febrile neutropenia in patients with high-risk early breast cancer receiving dose-dense chemotherapy and, as primary prophylaxis, either pegfilgrastim 6 mg fixed dose on the same day as chemotherapy or filgrastim on days 2-10 of each cycle. Secondary objectives included the rate of severe neutropenia, treatment delays and dose reductions. METHODS: This was a nonrandomized matched case-control study with 214 patients receiving dose-dense chemotherapy. Each group receiving supportive therapy included 107 patients (pegfilgrastim and filgrastim groups). RESULTS: Fourteen patients (13%) in the pegfilgrastim group developed febrile neutropenia as compared to 1 patient (1%) in the filgrastim group (p = 0.001). No statistically significant differences regarding the rate of severe neutropenia, treatment delays and dose reductions were observed. CONCLUSION: The results demonstrate that pegfilgrastim administered as primary prophylaxis on the same day as dose-dense chemotherapy is less efficacious than filgrastim administered on days 2-10 of each chemotherapy cycle. For the particular regimens given in this retrospective matched case-control study, the current recommendation for administering pegfilgrastim at least 24 h after chemotherapy completion seems justified. However, further randomized controlled trials are needed to clarify this finding.

Primary Alveolar Rhabdomyosarcoma of the Breast in an Adult: An Extremely Rare Case.

Sarcomas of the breast constitute less than 1% of all malignant breast tumors and primary rhabdomyosarcoma (RMS) is a very rare entity with limited case reports in the literature. RMS is common in children and adolescents and rare in adults. Primary RMS arising from the breast is exceedingly rare in adults. We report a case of a primary RMS of the breast in a 60-year-old woman, who presented in an early stage, mimicking invasive ductal carcinoma clinically and is in complete remission after three years of diagnosis and one year of treatment.

Paclitaxel- and platinum-based postoperative chemotherapy for primary fallopian tube carcinoma: a single institution experience.

BACKGROUND: Primary fallopian tube carcinoma (PFTC) is a rare gynecologic malignancy with very few data existing on the activity of the combination of paclitaxel with a platinum analogue as adjuvant chemotherapy. METHODS: We retrospectively analyzed 41 consecutive patients with PFTC who were treated postoperatively with paclitaxel- and platinum-containing chemotherapy regimens. RESULTS: We observed 12 (63.2%) complete and 6 (31.6%) partial responses among 19 patients with measurable disease. The median time to disease progression (TTP) for all patients was 68 months. The median overall survival (OS) for all patients has not been reached yet. The median TTP was 84 months for patients with stage I/II disease and 34 months for patients with advanced disease (p = 0.017). Median OS has not been reached yet for patients with stage I/II PFTC, while it was 63.8 months for patients with stage III/IV disease (p = 0.002). Furthermore, OS has not been reached yet for patients with optimally debulked tumors, while it was 34.1 months for patients with residual disease >2 cm (p < 0.0001). CONCLUSION: Adjuvant platinum- and paclitaxel-based chemotherapy should be regarded as the standard treatment in patients with PFTC. Early stage disease and optimal debulking are associated with improved TTP and OS.

Two cases of complete response after imatinib mesylate treatment of advanced GIST.

BACKGROUND: Imatinib mesylate has undoubted efficacy in the treatment of advanced gastrointestinal stromal tumors (GISTs), but complete responses have only been reported rarely. CASE REPORT: A 47-year-old man with liver metastasis from GIST achieved a complete response after 7 months of treatment with imatinib and a 47-year old woman with local relapse of GIST on the stomach after gastrectomy, showed complete remission, 9 months after treatment with imatinib. CONCLUSION: Although the response rate is high in patients with advanced GIST treated with imatinib mesylate, complete responses remain rare. Several issues concerning its optimal administration need to be clarified, in order to improve its efficacy.

Efficacy of methotrexate/vinblastine/doxorubicin cisplatin combination in gemcitabine-pretreated patients with advanced urothelial cancer: a retrospective analysis.

OBJECTIVE: Second-line treatment options in advanced urothelial cancer are limited. We investigated the efficacy of a methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) combination after failure of gemcitabine/platinum chemotherapy. PATIENTS AND METHODS: Twenty-five patients with advanced urothelial cancer, who received second-line MVAC after first-line gemcitabine/cisplatin (n = 9) or gemcitabine/carboplatin (n = 16), were included in this retrospective analysis. RESULTS: Twenty-two patients (88%) relapsed within 6 months after first-line treatment. Following MVAC, there were 5 (20%) objective responses. Median follow-up was 20.2 months. Median progression-free survival (PFS) was 3.8 months (95% CI: 2.3-5.2), and median overall survival (OS) was 9 months (95% CI: 6.6-11.4). Eastern Cooperative Oncology Group performance status 0.1 versus 2 was associated with longer PFS (5 months versus 3.3 months, P = 0.049). Response or stabilization of disease during second-line chemotherapy predicted for a significantly longer PFS and OS (7.4 versus 3.5, P = 0.005; 15.5 versus 7, P = 0.046). CONCLUSIONS: Second-line MVAC chemotherapy may result in prolonged survival in some patients with refractory disease. Further research in this field is necessary.

Paclitaxel and carboplatin as neoadjuvant chemotherapy in patients with locally advanced breast cancer: A phase II Trial of the Hellenic Cooperative Oncology Group.

PURPOSE: This phase II study sought to evaluate the efficacy of the paclitaxel-carboplatin combination as neoadjuvant chemotherapy in patients with locally advanced breast cancer (LABC). PATIENTS AND METHODS: A total of 46 patients with LABC and inflammatory breast cancer (IBC) received 6 cycles of paclitaxel 175 mg/m2, followed by carboplatin, at an area under the curve of 6, before mastectomy. The primary endpoint constituted response to chemotherapy. We studied ERCC1 protein, microtubule-associated protein-tau, estrogen receptor, progesterone receptor, epidermal growth factor receptor (EGFR), HER2, and Ki-67 immunohistochemically in tissue microarray and whole-tissue sections. In addition, EGFR and HER2 gene status was assessed by fluorescence in situ hybridization. Predictive and prognostic molecular markers were retrospectively investigated. RESULTS: A total of 42 female patients were considered eligible. Forty percent had IBC. Twenty-five patients (60%) experienced a clinical response, and 4 patients (9.5%) experienced a pathologic complete response. Chemotherapy was well tolerated. After a median follow-up of 45 months (range, 8.8-64.8 months), the estimated 3-year progression-free survival (PFS) was 54%, and the 3-year overall survival (OS) was 66%. The overexpression of EGFR protein was associated with a lower response rate (0 vs. 67%; P = .023), whereas high Ki-67 expression, high-grade tumors, tumor stage T4, and triple-negative tumors were associated with poorer PFS. Only high-grade tumors were associated with a significantly shorter OS (P = .004). CONCLUSION: The combination of paclitaxel and carboplatin is an effective and well-tolerated regimen in female patients with LABC.

Mucinous but not clear cell histology is associated with inferior survival in patients with advanced stage ovarian carcinoma treated with platinum-paclitaxel chemotherapy.

BACKGROUND: Mucinous and clear cell histology have been associated with adverse prognosis in ovarian carcinomas. The authors compared the outcome of these subtypes with that of serous tumors in patients who were treated with combination paclitaxel/platinum at their center. METHODS: Four hundred twenty patients with histologically confirmed, serous (n = 367), mucinous (n = 24), or clear cell (n = 29) ovarian carcinomas, International Federation of Gynecology and Obstetrics stage III or IV disease, and who were treated with paclitaxel/platinum after cytoreductive surgery were included in this analysis. RESULTS: The median overall survival for each histological subtype was 47.7 months (95% confidence interval [CI], 37.7-57.7 months) for serous, 15.4 months (95% CI, 4.2-26.6 months) for mucinous, and 36.6 months (95% CI, 22.7-50.5 months) for clear cell carcinomas. Cox regression analysis showed that mucinous histology was an independent predictor of poor prognosis compared with serous tumors (hazard ratio, 0.360; 95% CI, 0.215-0.603; P = .001). In contrast, such a difference between clear cell and serous carcinomas was not found (P = .337). Median survival of patients with mucinous tumors and residual disease >2 cm was poor, averaging 7.1 months (95% CI, 4.6-9.6 months). CONCLUSIONS: Mucinous but not clear cell histology is associated with significantly worse prognosis in advanced ovarian cancer treated with combination platinum/paclitaxel. Different therapeutic strategies should be studied in this entity.