ABSTRACT
BACKGROUND: Many gastric cancer patients in Western countries are diagnosed as metastatic with a median overall survival of less than twelve months using standard chemotherapy. Innovative treatments, like targeted therapy or immunotherapy, have recently proved to ameliorate prognosis, but a general agreement on managing oligometastatic disease has yet to be achieved. An international multi-disciplinary workshop was held in Bertinoro, Italy, in November 2022 to verify whether achieving a consensus on at least some topics was possible. METHODS: A two-round Delphi process was carried out, where participants were asked to answer 32 multiple-choice questions about CT, laparoscopic staging and biomarkers, systemic treatment for different localization, role and indication of palliative care. Consensus was established with at least a 67% agreement. RESULTS: The assembly agreed to define oligometastases as a "dynamic" disease which either regresses or remains stable in response to systemic treatment. In addition, the definition of oligometastases was restricted to the following sites: para-aortic nodal stations, liver, lung, and peritoneum, excluding bones. In detail, the following conditions should be considered as oligometastases: involvement of para-aortic stations, in particular 16a2 or 16b1; up to three technically resectable liver metastases; three unilateral or two bilateral lung metastases; peritoneal carcinomatosis with PCI ≤ 6. No consensus was achieved on how to classify positive cytology, which was considered as oligometastatic by 55% of participants only if converted to negative after chemotherapy. CONCLUSION: As assessed at the time of diagnosis, surgical treatment of oligometastases should aim at R0 curativity on the entire disease volume, including both the primary tumor and its metastases. Conversion surgery was defined as surgery on the residual volume of disease, which was initially not resectable for technical and/or oncological reasons but nevertheless responded to first-line treatment.
Subject(s)
Consensus , Delphi Technique , Stomach Neoplasms , Humans , Stomach Neoplasms/pathology , Stomach Neoplasms/drug therapy , Stomach Neoplasms/therapy , Neoplasm Metastasis , Italy , Neoplasm StagingABSTRACT
BACKGROUND: Adrenocortical cancer (ACC) is a rare malignancy with a dismal prognosis. The treatment includes mitotane and EDP chemotherapy (etoposide, doxorubicin, and cisplatin). However, new therapeutic approaches for advanced ACC are needed, particularly targeting the metastatic process. Here, we deepen the role of progesterone as a new potential drug for ACC, in line with its antitumoral effect in other cancers. METHODS: NCI-H295R, MUC-1, and TVBF-7 cell lines were used and xenografted in zebrafish embryos. Migration and invasion were studied using transwell assays, and MMP2 activity was studied using zymography. Apoptosis and cell cycle were analyzed by flow cytometry. RESULTS: Progesterone significantly reduced xenograft tumor area and metastases formation in embryos injected with metastatic lines, MUC-1 and TVBF-7. These results were confirmed in vitro, where the reduction of invasion was mediated, at least in part, by the decrease in MMP2 levels. Progesterone exerted a long-lasting effect in metastatic cells. Progesterone caused apoptosis in NCI-H295R and MUC-1, inducing changes in the cell-cycle distribution, while autophagy was predominantly activated in TVBF-7 cells. CONCLUSION: Our results give support to the role of progesterone in ACC. The involvement of its analog (megestrol acetate) in reducing ACC progression in ACC patients undergoing EDP-M therapy is now under investigation in the PESETA phase II clinical study.
Subject(s)
Adrenal Cortex Neoplasms , Adrenocortical Carcinoma , Animals , Humans , Adrenocortical Carcinoma/pathology , Progesterone/pharmacology , Progesterone/therapeutic use , Matrix Metalloproteinase 2 , Zebrafish , Cell Line, Tumor , Adrenal Cortex Neoplasms/metabolismABSTRACT
BACKGROUND: A difficulty score for laparoscopic adrenalectomy (LA) is lacking in the literature. A retrospective cohort study was designed to develop a preoperative "difficulty score" for LA. METHODS: A multicenter study was conducted involving four Italian tertiary centers for adrenal disease. The population was randomly divided into two subsets: training group and validation one. A multicenter study was undertaken, including 964 patients. Patient, adrenal lesion, surgeon's characteristics, and the type of procedure were studied as potential predictors of target events. The operative time (pOT), conversion rate (cLA), or both were used as indicators of the difficulty in three multivariate models. All models were developed in a training cohort (70% of the sample) and validated using 30% of patients. For all models, the ability to predict complicated postoperative course was reported describing the area under the curve (AUCs). Logistic regression, reporting odds ratio (OR) with p-value, was used. RESULTS: In model A, gender (OR 2.04, p = 0.001), BMI (OR 1.07, p = 0.002), previous surgery (OR 1.29, p = 0.048), site (OR 21.8, p < 0.001) and size of the lesion (OR 1.16, p = 0.002), cumulative sum of procedures (OR 0.99, p < 0.001), extended (OR 26.72, p < 0.001) or associated procedures (OR 4.32, p = 0.015) increased the pOT. In model B, ASA (OR 2.86, p = 0.001), lesion size (OR 1.20, p = 0.005), and extended resection (OR 8.85, p = 0.007) increased the cLA risk. Model C had similar results to model A. All scores obtained predicted the target events in validation cohort (OR 1.99, p < 0.001; OR 1.37, p = 0.007; OR 1.70, p < 0.001, score A, B, and C, respectively). The AUCs in predicting complications were 0.740, 0.686, and 0.763 for model A, B, and C, respectively. CONCLUSION: A difficulty score based on both pOT and cLA (Model C) was developed using 70% of the sample. The score was validated using a second cohort. Finally, the score was tested, and its results are able to predict a complicated postoperative course.
Subject(s)
Adrenal Gland Neoplasms , Laparoscopy , Adrenal Gland Neoplasms/pathology , Adrenal Gland Neoplasms/surgery , Adrenalectomy/methods , Cohort Studies , Humans , Laparoscopy/methods , Operative Time , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Retrospective StudiesABSTRACT
BACKGROUND: The present study provides a snapshot of Italian patients with peritoneal metastasis from gastric cancer treated by surgery in Italian centers belonging to the Italian Research Group on Gastric Cancer. Prognostic factors affecting survival in such cohort of patients were evaluated with the final aim to identify patients who may benefit from radical intent surgery. METHODS: It is a multicentric retrospective study based on a prospectively collected database including demographics, clinical, surgical, pathological, and follow-up data of patients with gastric cancer and synchronous macroscopic peritoneal metastases. Patients were surgically treated from January 2005 to January 2017. We focused on patients with macroscopic peritoneal carcinomatosis (PC) treated with upfront surgery in order to provide homogeneous evidences. RESULTS: Our results show that patients with peritoneal carcinomatosis cannot be considered all lost. Strictly selected cases (R0/R1 and P1 patients) could benefit from an aggressive surgical approach performing an extended lymphadenectomy and HIPEC treatment. CONCLUSION: The main result of the study is that GC patients with limited peritoneal involvement can have a survival benefit from a surgery with "radical oncological intent", that means extended lymphadenectomy and R0 resection. The retrospective nature of this study is an important bias, and for this reason, we have started a prospective multicentric study including Italian stage IV patients that hopefully will give us more answers.
Subject(s)
Hyperthermia, Induced , Peritoneal Neoplasms , Stomach Neoplasms , Humans , Italy/epidemiology , Peritoneal Neoplasms/surgery , Prognosis , Prospective Studies , Retrospective Studies , Stomach Neoplasms/surgeryABSTRACT
BACKGROUND: Outside the US, FLS certification is not required and its teaching methods are not well standardized. Even if the FLS was designed as "stand alone" training system, most of Academic Institution offer support to residents during training. We present the first systematic application of FLS in Italy. Our aim was to evaluate the role of mentoring/coaching on FLS training in terms of the passing rate and global performance in the search for resource optimization. METHODS: Sixty residents in general surgery, obstetrics & gynecology, and urology were selected to be enrolled in a randomized controlled trial, practicing FLS with the goal of passing a simulated final exam. The control group practiced exclusively with video material from SAGES, whereas the interventional group was supported by a mentor. RESULTS: Forty-six subjects met the requirements and completed the trial. For the other 14 subjects no results are available for comparison. One subject for each group failed the exam, resulting in a passing rate of 95.7%, with no obvious differences between groups. Subgroup analysis did not reveal any difference between the groups for FLS tasks. CONCLUSION: We confirm that methods other than video instruction and deliberate FLS practice are not essential to pass the final exam. Based on these results, we suggest the introduction of the FLS system even where a trained tutor is not available. This trial is the first single institution application of the FLS in Italy and one of the few experiences outside the US. Trial Number: NCT02486575 ( https://www.clinicaltrials.gov ).
Subject(s)
Clinical Competence , Internship and Residency/methods , Laparoscopy/education , Mentoring , Female , Humans , Italy , Male , Self-Directed Learning as Topic , Simulation Training/methods , Single-Blind Method , United StatesABSTRACT
This article reports the guidelines for gastric cancer staging and treatment developed by the GIRCG, and contains comprehensive indications for clinical management, including radiological, endoscopic, surgical, pathological, and oncological paths.
Subject(s)
Stomach Neoplasms/pathology , Stomach Neoplasms/therapy , Combined Modality Therapy , Humans , Italy , Neoplasm Staging , Prognosis , Stomach Neoplasms/classification , Time FactorsABSTRACT
BACKGROUND AND OBJECTIVE: Different components of the immune system, including innate and adaptive immunity (T effector lymphocytes and T regulatory lymphocytes - TREGs) may be involved in the development of hypertension, vascular injury and inflammation. However, no data are presently available in humans about possible relationships between T-lymphocyte subtypes and microvascular oxidative stress. Our objective was to investigate possible relationships between T-lymphocyte subtypes and systemic and microvascular oxidative stress in a population of normotensive subjects and hypertensive patients. PATIENTS AND METHODS: In the present study we enrolled 24 normotensive subjects and 12 hypertensive patients undergoing an elective surgical intervention. No sign of local or systemic inflammation was present. All patients underwent a biopsy of subcutaneous fat during surgery. A peripheral blood sample was obtained before surgery for assessment of T lymphocyte subpopulations by flow cytometry and circulating indices of oxidative stress. RESULTS: A significant direct correlation was observed between Th1 lymphocytes and reactive oxygen species (ROS) production (mainly in microvessels). Additionally, significant inverse correlations were observed between ROS and total TREGs, or TREGs subtypes. Significant correlations were detected between circulating indices of oxidative stress/inflammation and indices of microvascular morphology/Th1 and Th17 lymphocytes. In addition, a significant inverse correlation was detected between TREGs in subcutaneous small vessels and C reactive protein. CONCLUSIONS: Our data suggest that TREG lymphocytes may be protective against microvascular damage, probably because of their anti-oxidant properties, while Th1-Th17 lymphocytes seem to exert an opposite effect, confirming an involvement of adaptive immune system in microvascular damage.
Subject(s)
CD4-Positive T-Lymphocytes/metabolism , Oxidative Stress/physiology , Female , Humans , Male , Middle AgedABSTRACT
PURPOSE: Management of patients with synchronous hepatic metastases as the sole metastatic site at diagnosis of gastric cancer is debated. We studied a cohort of patients admitted to surgical units, investigating prognostic factors of clinical relevance and the results of various therapeutic strategies. METHODS: Retrospective multicentre chart review. We evaluated how survival from surgery was influenced by patient-related, gastric cancer-related, metastasis-related and treatment-related candidate prognostic factors. RESULTS: Forty-four patients received palliative surgery without resection, 98 palliative gastrectomy (in 16 cases associated with R+ hepatectomy), whereas 53 patients received both curative gastrectomy and hepatic resection(s) (R0). Adjuvant chemotherapy was administered to 44 patients. Therapeutic approach was selected on the basis of extension of disease, patient's general conditions and surgeon's attitude. Surgical mortality was 4.6 % and morbidity was 17.4 %. Survival was independently influenced by the factor T of the gastric primary (p = 0.036) and by the degree of hepatic involvement (p = 0.010). T > 2 and H3 liver involvement were associated with worse prognosis with cumulative effect (p = 0.002). Therapeutic approach to the metastases (p = 0.009) and adjuvant chemotherapy (p < 0.001) displayed independent impact upon survival, with benefit for those receiving aggressive multimodal treatment. The 1-, 3-, and 5-year survival rates were 50.4, 14.0, and 9.3 %, respectively, for patients submitted to curative surgery, 16, 8.5, and 4.3 % after palliative gastrectomy, and 6.8, 2.3, and 0 % after palliative surgery without resection. CONCLUSIONS: Our data suggest some clinical criteria that may facilitate selection of candidates to curative surgery, which offers the best survival chances, especially when associated with adjuvant chemotherapy.
Subject(s)
Liver Neoplasms/surgery , Neoplasms, Multiple Primary/surgery , Stomach Neoplasms/surgery , Aged , Chemotherapy, Adjuvant , Female , Gastrectomy , Hepatectomy , Humans , Liver Neoplasms/secondary , Liver Neoplasms/therapy , Male , Neoplasms, Multiple Primary/secondary , Neoplasms, Multiple Primary/therapy , Palliative Care , Prognosis , Retrospective Studies , Stomach Neoplasms/pathology , Survival AnalysisABSTRACT
PURPOSE: The purpose of the present study was to analyze clinicopathologic features and long-term prognosis of gastric stump cancer (GSC) arising in the remnant stomach 5 years or later after partial gastrectomy for benign disease. METHODS: We reviewed the results of 176 patients resected with curative intent for GSC at 8 Italian centers belonging to the Italian Research Group for Gastric Cancer (GIRCG). The median (range) follow-up time for surviving patients was 71.2 (6-207) months. RESULTS: One hundred forty-six patients were men, the mean age at the time of diagnosis was 69.2 years, and the great majority (167 cases) underwent Billroth II reconstruction. R0 resection was achieved in 158 (90 %) patients, and in 94 (53 %) lymph node dissection was ≥D2. Postoperative mortality and complication rates were 6.2 and 43.2 %, respectively. T1 tumor was diagnosed in 45 (25 %) cases. Lymph node metastases were evident in 86 patients (49 %). Thirteen patients had involvement of the jejunal mesentery nodes (pJN+); five cases were T2-T3 and eight cases were T4. Overall 5-year survival rate was 53.1 %. Five-year survival rates were 68.1, 37.8, and 33.1 % for pT1, pT2-3, and pT4 tumors, respectively (P = 0.001). Five-year survival rate was 56.5 % for node-negative tumors (pN0), 32.3 % for tumors with nodal metastases without involvement of jejunal mesentery nodes (pN+), and 17.1 % for tumors with involvement of jejunal mesentery nodes (pJN+) (P = 0.002). CONCLUSIONS: Our study suggests that an aggressive surgical approach can achieve a satisfactory outcome in GSC.
Subject(s)
Gastrectomy/adverse effects , Gastric Stump/pathology , Lymph Node Excision/adverse effects , Neoplasm, Residual/pathology , Postoperative Complications/pathology , Precancerous Conditions/surgery , Stomach Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Follow-Up Studies , Gastric Stump/surgery , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Neoplasm, Residual/etiology , Neoplasm, Residual/mortality , Postoperative Complications/etiology , Postoperative Complications/mortality , Precancerous Conditions/mortality , Precancerous Conditions/pathology , Prognosis , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Survival RateABSTRACT
PURPOSE: This study aims to recognize factors affecting operative and postoperative outcomes in patients undergoing unilateral laparoscopic adrenalectomy performed by using the transabdominal approach. METHODS: From a prospectively collected adrenal database, we performed a retrospective analysis of all patients undergoing unilateral adrenalectomy from July 2002 to December 2011. The outcome measures considered were the following: conversion rate, intra- and postoperative complications, duration of surgery, length of hospital stay, and return-to-work time. Demographic data, American Society of Anesthesiologists score, characteristics of adrenal tumor, and operative and postoperative variables were analyzed to assess their influence on the outcome variables. RESULTS: A total of 163 laparoscopic adrenalectomies were included. Intraoperative complications, conversion to laparotomy, and postoperative complications were observed in 6.7, 6.1, and 1.8 % of cases, respectively. Conversion to open surgery, intraoperative complications, metastasis, and pheochromocytoma were found to be predictive factors for operative time of >140 min. An operative duration of >140 min was associated with intraoperative complications. Tumor size, intraoperative complications, and adrenalectomy for metastasis significantly increased conversion rate. Hospital stay was extended by operative time of >140 min, conversion to laparotomy, and postoperative complications. CONCLUSION: Our study highlights that simple clinical variables, long procedures, and operative complications have a negative impact on procedural outcomes. Based on this, it may be possible to predict cases requiring collaboration with experienced surgeons in order to minimize perioperative morbidity.
Subject(s)
Adrenal Gland Diseases/surgery , Adrenalectomy , Laparoscopy/methods , Female , Humans , Intraoperative Complications/epidemiology , Length of Stay/statistics & numerical data , Male , Middle Aged , Operative Time , Postoperative Complications/epidemiology , Retrospective Studies , Return to Work , Treatment OutcomeABSTRACT
(1) Background: The standard first-line therapy for advanced adrenocortical carcinoma (ACC) is represented by EDP-M (etoposide, doxorubicin, cisplatin + mitotane). Progestins have shown cytotoxic activity both in vitro and in vivo on ACC; better EDP-M tolerability and efficacy have been hypnotized due to the association with progestins. (2) Methods: The feasibility and tolerability of EDP-M combined with oral megestrol acetate (EDP-MM) were tested in 24 patients (pts) affected by metastatic ACC with a low performance status (PS); the case group was compared with a 48 pts control group according to the propensity score. The secondary objectives were clinical benefit rate (CBR), progression-free survival (PFS), and overall survival (OS). (3) Results: Thirteen pts (54.2%) in the EDP-MM population experienced progestin-related toxicities; in particular, five pts experienced vaginal bleeding (20.8%); four pts experienced weight gain (16.7%); and thromboembolic events, worsening of hypertension, skin rashes, and hyperglycemia were registered in one patient each (4.2%). This led to the discontinuation of megestrol acetate in four pts (16.7%). EDP-M-related toxicities were similar in both groups. No differences in PFS and OS curves were observed; the CBR was 75.0% and 60.4%, respectively. (4) Conclusions: The association of EDP-M + megestrol acetate in ACC pts with a low PS is feasible and well tolerated; its efficacy appeared to be non-inferior to EDP-M administered to pts with a good PS.
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The pharmacological approach to adrenocortical carcinoma (ACC) is based on mitotane with/without etoposide, doxorubicin, and cisplatin, according to the disease stage. Considering the limited efficacy and toxicity of this treatment, new strategies are required. Trabectedin is a marine-derivated antitumoral agent that inhibits oncogenic transcription. We have already demonstrated trabectedin cytotoxic activity at sub-nanomolar concentrations in ACC cells. Here, we expanded the investigation of trabectedin effect on ACC preclinical models, evaluating whether trabectedin could affect ACC cells' invasiveness and metastasis formation. NCI-H295R, MUC-1, and TVBF-7 cell lines were used. Cell tumor xenografts in Danio rerio embryos were performed. The tumor mass areas and the number of embryos with metastasis were evaluated. The in vitro invasiveness of cells was evaluated. Effects of trabectedin of MMP2, TIMP1, and TIMP2 were evaluated at gene level qRT-PCR. MMP2 secreted in the cell medium was evaluated by Western blot and by zymography. Xenograft experiments demonstrated that trabectedin significantly reduced the tumor area in each ACC cell model and metastasis formation in embryos injected with metastasis-derived cell lines. Trabectedin treatment reduced the invasiveness of ACC cells across the matrix, which was greater at baseline for the metastatic models. In metastatic cell models, protein analysis demonstrated a reduction of MMP2 secretion and activity in the culture medium after treatment. Our results indicate that trabectedin interferes with invasiveness and metastasis processes, both dramatic features of ACC. Furthermore, these results support those previously published in providing the rationale for a clinical evaluation of the efficacy of trabectedin in ACC patients.
Subject(s)
Adrenal Cortex Neoplasms , Adrenocortical Carcinoma , Humans , Adrenocortical Carcinoma/genetics , Trabectedin/therapeutic use , Matrix Metalloproteinase 2 , Adrenal Cortex Neoplasms/genetics , Cell Line, TumorABSTRACT
BACKGROUND: The coronavirus pandemic had a major impact in Italy. The Italian health system's re-organization to face the emergency may have led to significant consequences especially in the diagnosis and treatment of malignancies. This study aimed to assess the impact of the pandemic in the diagnosis and treatment of gastric cancer in nine Gruppo Italiano RIcerca Cancro Gastrico (GIRCG) centers. METHODS: All patients assessed for gastric adenocarcinoma at nine GIRCG centers between January 2019 and November 2020 were included. Patients were grouped according to the date of "patient 1's" diagnosis in Italy: preCOVID versus COVID. Clinico-pathological and outcome differences between the two groups were analyzed. RESULTS: A total of 632 patients were included in the analysis (205 in the COVID group). The cT4 weighted ratios were higher in 2020 from April to September, with the greatest differences in May, August and September. The cM+ weighted ratio was significantly higher in July 2020. The mean number of gastrectomies had the greatest reduction in March and May 2020 compared with 2019. The median times from diagnosis to chemotherapy, to complete diagnostic work-up or to operation were longer in 2019. The median time from the end of chemotherapy to surgery was 17 days longer in the preCOVID group. CONCLUSIONS: A greater number of advanced or metastatic cases were diagnosed after the spread of SARS-CoV-2 infection, especially after the "full lockdown" periods. During the pandemic, once gastric cancer patients were referred to one of the centers, a shorter time to complete the diagnostic work-up or to address them to the best treatment option was required.
Subject(s)
COVID-19 , Stomach Neoplasms , Humans , COVID-19/epidemiology , Pandemics , SARS-CoV-2 , Stomach Neoplasms/diagnosis , Stomach Neoplasms/epidemiology , Stomach Neoplasms/therapy , Communicable Disease Control , Italy/epidemiology , Referral and Consultation , COVID-19 TestingABSTRACT
BACKGROUND: Interest in the field of metastatic gastric cancer has grown in recent years, and the identification of oligometastatic patients plays a critical role as it consents to their inclusion in multimodal treatment strategies, which include systemic therapy but also surgery with curative intent. To collect sound clinical data on this subject, The Italian Research Group on Gastric Cancer developed a prospective multicentric observational register of metastatic gastric cancer patients called META-GASTRO. METHODS: Data on 383 patients in Meta-Gastro were mined to help our understanding of oligometastatic, according to its double definition: quantitative/anatomical and dynamic. RESULTS: the quantitative/anatomical definition applies to single-site metastases independently from the metastatic site (p < 0.001) to peritoneal metastases with PCI ≤ 12 (p = 0.009), to 1 or 2 hepatic metastases (p = 0.024) and nodal metastases in station 16 (p = 0.002). The dynamic definition applies to a percentage of cases variable according to the metastatic site: 8%, 13.5 and 23.8% for hepatic, lymphatic and peritoneal sites, respectively. In all cases, the OS of patients benefitting from conversion therapy was similar to those of cases deemed operable at diagnosis and operated after neoadjuvant chemotherapy. CONCLUSIONS: META-GASTRO supports the two-fold definition of oligometastatic gastric cancer: the quantitative/anatomical one, which accounts for 30% of our population, and the dynamic one, observed in 16% of our cases.
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Adrenocortical carcinoma (ACC) is an extremely rare disease, the incidence of which is 0 [...].
ABSTRACT
Etoposide, doxorubicin and cisplatin plus oral mitotane (EDP-M) comprise the reference regimen in the management of patients with adrenocortical carcinoma (ACC). In this paper, we described the outcome of 58 patients with advanced/metastatic ACC consecutively treated with EDP-M in a reference center for this rare disease in Italy. In this series, EDP-M obtained a partial response in 50% of patients; median progression free survival (PFS) and overall survival were 10.1 months (95% Confidence Interval [CI 95%] 8.1-12.8) and 18.7 months (95% CI: 14.6-22.8), respectively. EDP-M was not interrupted in five patients showing disease progression after two cycles without the appearance of new lesions and mitotane levels below the therapeutic range. In two of them, the disease remained stable at further imaging evaluations and the other three obtained a partial response. Twenty-six responding patients underwent surgery of residual disease and 13 of them became disease free. Surgery identified a pathological complete response (pCR) in four patients (7%) and Ki67 expression in post-chemotherapy tumor specimens, inferior to 15% (median value), was associated with better PFS and survival. In the present study, the EDP-M regimen is confirmed to have a limited efficacy. Early disease progression does not mean treatment inefficacy. Surgery of residual disease in partially responding patients allows for the detection of pCR in few of them and this condition is predictive of long-term survival. Ki67 expression of post-chemotherapy residual disease could be an additional prognostic factor that deserves to be studied further.
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We evaluated tumor response at Computed Tomography (CT) according to three radiologic criteria: RECIST 1.1, CHOI and tumor volume in 34 patients with metastatic adrenocortical carcinoma (ACC) submitted to standard chemotherapy. These three criteria agreed in defining partial response, stable or progressive disease in 24 patients (70.5%). Partial response (PR) was observed in 29.4%, 29.4% and 41.2% of patients according to RECIST 1.1, CHOI and tumor volume, respectively. It was associated with a favorable prognosis, regardless of the criterion adopted. The concordance of all the 3 criteria in defining the disease response identified 8 patients (23.5%) which displayed a very good prognosis: median progression free survival (PFS) and overall survival (OS) 14.9 and 37.7 months, respectively. Seven patients (20.6%) with PR assessed by one or two criteria, however, still had a better prognosis than non-responding patients, both in terms of PFS: median 12.3 versus 9.9 months and OS: 21 versus 12.2, respectively. In conclusions, the CT assessment of disease response of ACC patients to chemotherapy with 3 different criteria is feasible and allows the identification of a patient subset with a more favorable outcome. PR with at least one criterion can be useful to early identify patients that deserve continuing the therapy.
ABSTRACT
BACKGROUND: This study explores the impact of Hypertermic Intra PEritoneal Chemotherapy (HIPEC) on adrenocortical carcinoma (ACC) management through a safety analysis completed by a preliminary evaluation of survival performances. METHODS: Retrospective chart review of 27 patients submitted to surgical treatment completed by HIPEC for primary (SP, 13 patients) or recurrent (SR, 14 patients, 17 treatments) ACC. Safety was evaluated by means of procedural morbidity and mortality. Survival performances included multiple end points: local/peritoneal disease-free survival (l/pDFS), overall progression-free survival (OPFS), and overall survival (OS). RESULTS: In the SP group, mortality was nil and morbidity was 46% (major 23%). At a median follow-up of 25 months, the median value for all the different survival measures had not been reached. Mortality was also nil in the SR group. However, morbidity was 77% (major 18%). Median l/pDFS and OPFS were 12 ± 4 and 8 ± 2 months, respectively. At a median follow-up of 30 months, median OS had not been reached. CONCLUSION: Surgery and HIPEC is an invasive procedure. Its employment in the surgery for primary setting deserves attention as it may affect oncologic outcomes positively. Its value in the management of recurrences seems less appreciable, albeit it may find its place in the multimodal management of a rare disease for which multiple therapeutic options do not yet exist.