Contemporary outcomes of metastatic breast cancer among 22,000 women from the multicentre ESME cohort 2008-2016.

AIM: Real-world data inform the outcome comparisons and help the development of new therapeutic strategies. To this end, we aimed to describe the full characteristics and outcomes in the Epidemiological Strategy and Medical Economics (ESME) cohort, a large national contemporary observational database of patients with metastatic breast cancer (MBC). METHODS: Women aged ≥18 years with newly diagnosed MBC and who initiated MBC treatment between January 2008 and December 2016 in one of the 18 French Comprehensive Cancer Centers (N = 22,109) were included. We assessed the full patients' characteristics, first-line treatments, overall survival (OS) and first-line progression-free survival, as well as updated prognostic factors in the whole cohort and among the 3 major subtypes: hormone receptor positive and HER2-negative (HR+/HER2-, n = 13,656), HER2-positive (HER2+, n = 4017) and triple-negative (n = 2963) tumours. RESULTS: The median OS of the whole cohort was 39.5 months (95% confidence interval [CI], 38.7-40.3). Five-year OS was 33.8%. OS differed significantly between the 3 subtypes (p < 0.0001) with a median OS of 43.3 (95% CI, 42.5-44.5) in HR+/HER2-; 50.1 (95% CI, 47.6-53.1) in HER2+; and 14.8 months (95% CI, 14.1-15.5) in triple-negative subgroups, respectively. Beyond performance status, the following variables had a constant significant negative prognostic impact on OS in the whole cohort and among subtypes: older age at diagnosis of metastases (except for the triple-negative subtype), metastasis-free interval between 6 and 24 months, presence of visceral metastases and number of metastatic sites ≥ 3. CONCLUSIONS: The ESME program represents a unique large-scale real-life cohort on MBC. This study highlights important situations of high medical need within MBC patients. DATABASE REGISTRATION: clinicaltrials.gov Identifier NCT032753.

Outcomes of complex abdominal wall reconstruction at the time of CRS and HIPEC.

INTRODUCTION: Cytoreduction Surgery with Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC) is a treatment option for patients with peritoneal metastatic cancer. This procedure has been shown to improve survival, however, patients are often left with abdominal wall and soft tissue defects requiring further surgical correction. We aim to assess the safety and clinical outcomes of abdominal reconstruction performed concurrent with CRS/HIPEC. METHODS: We conducted a retrospective chart review on patients with peritoneal metastases who received CRS/HIPEC therapy and abdominal wall reconstruction at tertiary center from 2012 to 2018. Records were evaluated for the patient characteristics, oncologic history, operative details, and postoperative course. Complications were graded with the Clavien-Dindo classification. RESULTS: Five patients aged 29-54 years old met the inclusion criteria. The most common type of cancer within this cohort was colorectal cancer. To close the abdomen, four patients underwent component release, biologic mesh placement, and primary fascial closure. The last patient was closed with adjacent tissue transfer. Two patients experienced Grade I complications: deep vein thrombosis and leukocytosis (both self-resolved). Three patients experienced Grade II complications: atrial fibrillation, anemia, and a wound infection which required readmission. No patients experienced grades III, IV or V complications. The follow up period was a median of 5.3 months [r: 2.6-21.9 months]. CONCLUSION: The patients benefitted therapeutically from combined abdominal reconstruction and CRS/HIPEC with minimal complications and good long-term survival. We advocate for the coupling of these procedures as the benefits outweigh the risks, and allows wound closure at the time of surgery.

Allogenic Blood Transfusion Is an Independent Predictor of Poorer Peri-operative Outcomes and Reduced Long-Term Survival after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: a Review of 936 Cases.

INTRODUCTION: There is a paucity of data on the impact of allogenic blood transfusion (ABT) on morbidity and survival outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). METHODS: Nine hundred and thirty-five consecutive CRS/HIPEC procedures were performed between 1996 and 2016 at a high-volume institution in Sydney, Australia. Of these, 337(36%) patients required massive ABT (MABT) (≥5 units). Peri-operative complications were graded according to the Clavien-Dindo classification. The association of concomitant MABT with 21 peri-operative outcomes and overall survival (OS) was assessed using univariate and multivariate analyses. RESULTS: In-hospital mortality was 1.8%. Patients requiring MABT had more extensive disease as reflected by a higher peritoneal cancer index (≥17) (70 vs. 29%, p < 0.001) and longer operative times (≥9 h) (82 vs. 35%, p < 0.001). After accounting for confounding factors, MABT was associated with in-hospital mortality (relative risk (RR), 7.72; 95% confidence interval (CI), 1.35-10.11; p = 0.021) and grade III/IV morbidity (RR, 2.05; 95% CI, 1.42-2.95; p < 0.001). MABT was associated with an increased incidence of prolonged hospital stay (≥28 days) (RR, 1.86; 95% CI, 1.26-2.74; p = 0.002) and intensive care unit stay (≥4 days) (RR, 1.83; 95% CI, 1.24-2.70, p = 0.002). It was also associated with a significant OS in patients with colorectal cancer peritoneal carcinomatosis (RR 4.49; p < 0.001) and pseudomyxoma peritonei (RR, 4.37; p = 0.026), but not appendiceal cancer (p = 0.160). CONCLUSION: MABT is an independent predictor for poorer peri-operative outcomes including in-hospital mortality and grade III/IV morbidity. It may also compromise long-term survival, particularly in patients with colorectal cancer peritoneal carcinomatosis.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for gallbladder cancer: a retrospective review.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) often prolongs survival in patients with peritoneal surface disease, yet is generally avoided in patients with peritoneal spread from gallbladder cancer as a result of its aggressive biologic behavior. Therefore, we reviewed our experience with CRS/HIPEC for patients with gallbladder cancer. We retrospectively evaluated the outcomes of CRS/HIPEC procedures performed from 1991 to 2013 using a prospectively maintained database of 1069 procedures. Patient and tumor characteristics, morbidity, mortality, and survival were reviewed. CRS/HIPEC was performed six times in five patients with peritoneal spread from gallbladder cancer. Patients were young (age 28 to 54 years) without pre-existing comorbidities. Eighty per cent had an Eastern Cooperative Oncology Group score of 0 or 1. At CRS, organs resected included omentum (n = 4), liver (n = 3), colon (n = 2), ovaries (n = 1), and diaphragm (n = 1). A complete macroscopic cytoreduction of intraperitoneal disease was achieved in every case. Clavien graded major morbidity was 17 per cent. There was no observed mortality. Median and 3-year survival were 22.4 months and 30 per cent, respectively. CRS/HIPEC may be performed safely in patients with peritoneal dissemination from gallbladder cancer. Carefully selected patients with low-volume disease amenable to complete cytoreduction may experience a meaningful survival benefit.

[Operative therapy of abdominal and retroperitoneal sarcoma]. / Operative Therapie der abdominellen und retroperitonealen Sarkome.

Retroperitoneal soft tissue sarcomas are characterized by a high rate of local recurrence. Complete tumor resection is the only potentially curative therapeutic option. The concept of a systematic compartmental resection is to remove the tumor en bloc with a margin of uninvolved tissue and organs. This is frequently only achieved by multivisceral resection which often includes kidney, colon, pancreas and parts of the diaphragm or the psoas muscle. The adoption of such a policy of multivisceral organ resection improves the proportion of curative resections and, ultimately, results in lower local recurrence rates. The present article comprehensively describes the operative procedures, perioperative treatment and the oncological results of surgery for retroperitoneal sarcomas. The role of surgery in oncological treatment plans and the importance of specialized centres are outlined in detail.

Can smaller-scale comprehensive cancer centers provide outstanding care in abdominal and thoracic pediatric solid tumor surgery? Results of a 14-year retrospective single-center analysis.

PURPOSE: Quality of care and its measurement represent a considerable challenge for pediatric smaller-scale comprehensive cancer centers (pSSCC) providing surgical oncology services. It remains unclear whether center size and/or yearly case-flow numbers influence the quality of care, and therefore impact outcomes for this population of patients. PATIENTS AND METHODS: We performed a 14-year, retrospective, single-center analysis, assessing adherence to treatment protocols and surgical adverse events as quality indicators in abdominal and thoracic pediatric solid tumor surgery. RESULTS: Forty-eight patients, enrolled in a research-associated treatment protocol, underwent 51 cancer-oriented surgical procedures. All the protocols contain precise technical criteria, indications, and instructions for tumor surgery. Overall, compliance with such items was very high, with 997/1,035 items (95 %) meeting protocol requirements. There was no surgical mortality. Twenty-one patients (43 %) had one or more complications, for a total of 34 complications (66 % of procedures). Overall, 85 % of complications were grade 1 or 2 according to Clavien-Dindo classification requiring observation or minor medical treatment. Case-sample and outcome/effectiveness data were comparable to published series. Overall, our data suggest that even with the modest caseload of a pSSCC within a Swiss tertiary academic hospital, compliance with international standards can be very high, and the incidence of adverse events can be kept minimal. CONCLUSION: Open and objective data sharing, and discussion between pSSCCs, will ultimately benefit our patient populations. Our study is an initial step towards the enhancement of critical self-review and quality-of-care measurements in this setting.

Updates on the multimodality management of desmoplastic small round cell tumor.

Desmoplastic Small Round Cell Tumor (DSRCT) is a rare and an aggressive malignancy with poor outcome. This tumor can co-express epithelial, neural, and mesenchymal markers. The molecular hallmark of DSRCT is the EWS-WT1 fusion protein. Despite the diversities in treatment modality, the best results have been seen with radical surgery and adjuvant or neoadjuvant chemotherapy.

[Intraoperative therapeutic intensification techniques in locally advanced abdominal sarcomas]. / Intensificación terapéutica intraoperatoria en el tratamiento de los sarcomas abdominales localmente avanzados.

INTRODUCTION: Sarcomas are rare tumors that develop from mesenchymal cells. Their management is difficult due to their changing histology, location, and behavior. In this article, we discuss the use of two intraoperative therapeutic intensification techniques, intraoperative radiotherapy (IORT) and hyperthermic intraoperative intraperitoneal chemotherapy (HIIC), in the treatment of locally advanced abdominal sarcomas and peritoneal sarcomatosis. MATERIAL AND METHODS: We analyzed a series of 20 consecutive patients diagnosed with advanced abdominal sarcoma and 5 patients with a diagnosis of peritoneal sarcomatosis who were evaluated and treated in our department from December 1996 to October 2005. In advanced abdominal sarcoma, we performed complete or maximal resection followed by IORT. In peritoneal sarcomatosis we performed massive cytoreduction followed by HIIC. RESULTS: The survival rate in advanced abdominal sarcomas without sarcomatosis was 65% at 26 months. Among the 5 patients diagnosed with peritoneal sarcomatosis, 3 were alive, and 2 were without recurrence at 20 months of follow-up. CONCLUSIONS: IORT associated with radical surgery seems to improve local control and survival in advanced abdominal sarcomas. Maximal cytoreduction plus HIIC used as treatment of peritoneal sarcomatosis is a feasible technique that offers a therapeutic option with curative intent.

Hyperthermic intraperitoneal intraoperative chemotherapy after cytoreductive surgery for the treatment of abdominal sarcomatosis: clinical outcome and prognostic factors in 60 consecutive patients.

BACKGROUND: Abdominal sarcomatosis is a rare nosologic entity with a poor prognosis. After a Phase I study on cytoreductive surgery combined with hyperthermic intraperitoneal intraoperative chemotherapy (HIIC), the authors reported the results of the treatment of 60 patients using this novel multimodal approach. METHODS: Twenty-nine patients had multifocal primary disease and 31 patients had recurrent abdominal sarcoma. Tumor histology was represented by visceral (n = 26 [43%]) and retroperitoneal (n = 34 [57%]) sarcoma. All patients underwent cytoreductive surgery (with no or minimal residual disease) and 90-minute HIIC with doxorubicin (15.25 mg/L of perfusate) and cisplatin (43 mg/L). The clinical outcome and the prognostic value of 11 clinicopathologic variables were analyzed. RESULTS: No postoperative deaths occurred. The morbidity rate was 33% and the moderate to severe locoregional toxicity rate was 15%. The median time to local disease progression and the median overall survival were 22 months and 34 months, respectively. Using multivariate analysis, histologic grading and completeness of surgical cytoreduction predicted patient prognosis, indicating that both local progression-free and overall survival were affected significantly by tumor aggressiveness and local disease control. CONCLUSIONS: Although these results were encouraging, there was no definitive conclusion reached regarding the therapeutic activity of this locoregional treatment. In addition, the toxicity rate was substantial. In the absence of effective systemic agents, the therapeutic potential of cytoreductive surgery plus HIIC should be explored further in comparative trials.

The impact of gross total resection on local control and survival in high-risk neuroblastoma.

BACKGROUND/PURPOSE: Gross total resection of the primary tumor in treatment of high-risk neuroblastoma remains controversial. Furthermore, there are few reports of the effect of primary tumor resection on local control as opposed to overall survival. The authors reviewed their institutional experience to assess the effect of primary tumor resection on local control and overall survival. METHODS: A total of 141 patients were treated on protocol between November 1, 1979 and June 25, 2002 and are the subject of this report. Gross total resection was assessed by review of operative notes, postoperative computerized axial tomograms, and postoperative meta-iodobenzyl guanidine (MIBG)1 scans when available. RESULTS: The median age was 3.3 years, and all patients were International Neuroblastoma Staging System (INSS) stage 4 with 79% having metastases to cortical bone. The primary site was the adrenal gland in 74%, the central abdominal compartment in 13%, the posterior mediastinum in 7%, and other sites in 6%. Gross total resection was accomplished in 103 (73%) but was more than 90% for the last 3 protocols. Five kidneys were lost overall. The probability of local progression was 50% in unresected patients compared with 10% in patients undergoing gross total resection (P <.01). Overall survival rate in resected patients was 50% compared with 11% in unresected patients (P <.01). CONCLUSIONS: Our data indicate that local control and overall survival rate are correlated with gross total resection of the primary tumor in high-risk neuroblastoma. Gross total resection should be part of the management of stage 4 neuroblastoma in patients greater than 1 year of age.

Rectal cancer and inguinal metastases: prognostic role and therapeutic indications.

PURPOSE: The aim of this study was to analyze the outcome of patients with inguinal metastases from rectal cancer. METHODS: Clinical records and data concerning the follow-up of patients referred to our institution for rectal cancer were reviewed retrospectively. Patients were divided into four groups based on the time interval between first admission and appearance of inguinal metastases. All patients were followed up until death. Age, gender, tumor stage, and disease-free intervals were examined to assess their impact on prognosis. RESULTS: Patients with rectal adenocarcinoma (N = 863) were observed from 1965 to 1990. In 21 patients the biopsy-proven diagnosis was of adenocarcinoma metastasizing to the inguinal nodes. Of these 21 patients, 15 were males. The mean age was 69.3 (range, 52-84) years. Primary lesions were exclusively T3, and no patient was found to have negative mesorectal lymph nodes. Survival from the time of diagnosis of inguinal metastases ranged from 2 to 42 (mean, 14.8) months. Patients with a disease-free interval of 12 months or more had a statistically significant longer survival time. CONCLUSIONS: Inguinal lymph-node metastases from rectal carcinoma occur as a consequence of locally advanced primary tumors or recurrent pelvic malignancy. Because of the frequency of distant metastases and the consequent poor prognosis, only systemic chemotherapy and radiotherapy should be considered. In patients who seem to be free of local recurrence and distant metastases, groin dissection is suggested for debulking and control of disease.

Peritonectomy combined with intraperitoneal chemohyperthermia in abdominal cancer with peritoneal carcinomatosis: phase I-II study.

OBJECTIVE: To evaluate the feasibility and the tolerance of Peritonectomy Procedure (PP) combined with Intraperitoneal Chemohyperthermia (IPCH) in patients with peritoneal carcinomatosis, a phase I-II study has been realised from January 1997 to September 1998. METHODS: Eighteen patients were included for peritoneal carcinomatosis from colorectal cancer (13), ovarian cancer (2), gallbladder cancer (1), gastric cancer (1) and peritoneal mesothelioma (1). Peritoneal carcinomatosis were mainly advanced disease (16 stage 3 and 4, 2 stage 2). All the patients underwent surgical resection of their primary tumor with PP as described by Sugarbaker and IPCH (with Mitomycin C, Cisplatinum or both). IPCH used in this study was a "closed sterile circuit" device with inflow temperatures ranging from 46 to 48 degrees C. IPCH was performed on the same day as PP (8118) or delayed (10/18). RESULTS: Significant down-staging of peritoneal carcinomatosis was achieved for 16 patients. One patient died postoperatively, while the morbidity rate was 6/18 (long postoperative ileus, grade 3 leucopenia and anastomotic leakage). CONCLUSIONS: Combination of PP and IPCH could achieve significant tumoral volume reduction in peritoneal carcinomatosis. This aggressive treatment must be employed selectively because of its morbidity. Larger phase III studies are now needed.

Chemohyperthermic peritoneal perfusion for peritoneal dissemination in various intra-abdominal malignancies.

A total of 25 patients with severe peritoneal dissemination underwent chemohyperthermic peritoneal perfusion (CHPP). The primary tumors in these patients comprised colorectal cancer (n = 14), ovarian cancer (n = 6), cervical cancer, (n = 1), small bowel cancer (n = 1), pseudomyxoma retroperitonei (n = 1), cystoadenocarcinoma of liver (n = 1), and pancreas cancer (n = 1). The intraperitoneal perfusion was carried out with a magnet pump for 60 min. The heated perfusate contained anticancer drugs to act synergistically with the hyperthermia. The intraperitoneal temperature was maintained at 42.0-42.5 degrees C. Eight of 25 patients showed CR, four PR, ten NC, and three PD, and the percentage (CR+PR) representing the overall efficacy rate was 48.0%. The morbidity rate was 8% (2/25) and there was no treatment-associated mortality. The percentage (CR+PR) of the patients with colorectal cancer was 57%; ovarian cancer, 50%; and other malignancies, 20%. The 1 year-and 3 year-survival rates of all the patients were 55% and 26%, respectively. The median survival periods of the CR, PR, NC, and PD groups were 4.0, 1.0, 1.0, and 0.7 years, respectively. The survival curve of the CR group was the best of all the groups (P = 0.02). These results indicated that CHPP was a feasible therapy and exerted a direct anticancer effect on peritoneal dissemination especially in the case of ovarian cancer, and the prognosis of complete responders was improved.

Treatment results in children and adolescents with loco-regional recurrences of abdominal germ cell tumors (GCTs): a pilot-study with PEI chemotherapy and regional deep hyperthermia (RHT) in comparison to a matched cohort.

In this study treatment results in children and adolescents (n = 32) suffering from loco-regional abdominal relapses of germ cell tumors (GCT) (7 embryonal carcinoma, 17 Yolk sac tumors, 8 immature teratomas) aged from 1;0 to 23;3 years (mean = 10;11 years) were evaluated. In this pilot study 9 patients were treated with cisplatinum (40 mg/m2 on days 1 and 4), etoposide (100 mg/m2 on days 1 to 4), and ifosfamide (2000 mg/m2 on days 1 to 4) (PEI) +/- radiation in combination with regional deep hyperthermia (RHI). In sedation RHT was induced by non-invasive heat applicators (Sigma-40 and Sigma 60, BSD Medical Corporation, Utah, USA). In 7 out of these 9 patients with recurrent GCT a tumor response (5 CR, 2 PR, 1 SD, 1 PD) was found. In addition, in 2 patients a complete tumor resection could be achieved inspite of 2 previous incomplete tumor resections each. Five out of 9 patients are living event-free after an observation period ranging from 8 to 40 months (median = 15 months). Treatment results of this RHT study population were compared with treatment results in patients with recurrent GCT, who received conventional relapse therapy (chemotherapy/ surgery +/- radiation) alone. In this matched cohort 5 out of 23 patients are living event-free after an observation time ranging from 1 to 120 months (median = 8 months). According to Kaplan-Maier life table analysis, patients with relapse therapy combined with RHT have an event-free survival (EFS) of 0.41 +/- 0.33 whereas the matched cohort without RHT have an EFS of 0.16 +/- 0.25. The difference in treatment results of both groups is significant (Wilcoxon/p = 0.03). From the data presented in this study we conclude that children with loco-regional recurrences of extracranial non-testicular GCT have an unfavorable prognosis, unless local tumor control can be achieved. The additional application of RHT in combination with conventional therapy (PEI chemotherapy +/- radiation) can improve local tumor control and EFS in GCT patients with loco-regional recurrences. Therefore, based upon these results in the future MAKEI trial RHT will be applied to GCT patients with poor response to neoadjuvant chemotherapy alone as first line treatment.

Recurrent intraabdominal cancer with intestinal obstruction.

The objective of this study was to evaluate short and long term results of management of recurrent intraabdominal malignancy causing intestinal obstruction using surgery and intraperitoneal chemotherapy and determine the clinical features that suggest favorable outcome. Forty two consecutive patients who were treated by cytoreductive surgery with or without intraperitoneal chemotherapy were retrospectively analyzed. There were 20 patients with primary tumors of appendix, 13 with cancer of colon or rectum, and 9 patients with cancer of other origins. All 42 patients were explored and extensively evaluated intraoperatively. Surgery included bowel resections and peritonectomy procedures. In 30 patients early postoperative intraperitoneal chemotherapy was administered. The overall morbidity was 55% while mortality was 7.14%. The projected three year survival for this group of patients was 32.7%. Among the most significant clinical features that reflect favorable prognosis were low histologic grade of malignancy, recurrence 2 and more years after primary surgery, and cancer that could be completely surgically excised. As a result of treatment patients' performance status improved in 47.6% of cases. An aggressive reoperative approach may be considered for palliation of selected patients with recurrent cancer causing intestinal obstruction.

Intraoperative radiation therapy and hyperthermia. Morbidity and mortality from this combined treatment modality for unresectable intra-abdominal carcinomas.

This is a report of a phase I trial of intraoperative radiation therapy in combination with intraoperative hyperthermia for the treatment of locally advanced, unresectable intra-abdominal carcinomas. Using an ultrasound transducer system specifically designed for intraoperative applications, 19 patients have been successfully treated, demonstrating the feasibility of this combination modality. The morbidity (58%) and mortality (11%) rates reported in this series are comparable to rates reported in series of similar patients receiving intraoperative radiation therapy alone. There is still a great need for considerable technological development to enable the use of intraoperative hyperthermia to treat large, complexly shaped intra-abdominal tumors, and phase II and III trials of this combination treatment modality should be performed.

Palliation of malignant ascites by the LeVeen peritoneo-venous shunt.

A LeVeen peritoneo-venous shunt was placed in each of 5 patients under local anesthesia to relieve symptomatic malignant ascites. All patients had marked ascites due to histologically documented intraabdominal carcinomatosis, extensive hepatic neoplasm, or a combination of malignant ascites and severe parenchymal liver disease. Cases included metastatic breast carcinoma, pancreatic carcinoma, melanoma, and primary cholangiocarcinoma. Prompt relief of respiratory distress and discomfort associated with tense ascites was achieved in all patients; however, survival was short (one week to seven months) due to advanced disease. The LeVeen shunt can provide effective palliation of malignant ascites in carefully selected symptomatic patients.