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Abstract Introduction/Objective Amplifications of the MDM2 gene is a well-recognized central molecular event in atypical lipomatous tumors, well-differentiated liposarcomas, and dedifferentiated liposarcomas. However, given the fact that most adipocytic neoplasms are benign, the specific testing approaches that will maximize the detection of MDM2 amplified tumors in an accurate and cost-efficient manner remains unclear. The purpose of this study is to present our experience with MDM2 testing by FISH in a large cohort of lipomatous neoplasms. Methods/Case Report The pathologic database of an academic medical center was queried for all lipomatous tumors as well as all tumors for which MDM2 testing was performed during a three-year period. At our center, MDM2 testing for well differentiated adipocytic neoplasms is triggered by the so-called “traditional criteria”: a deep tumor and/or tumor size >10 cm and/or recurrence. We also take an expanded approach for a variety of indications that may include equivocal atypia or clinical/imaging concern, among others. Testing is also performed on overt malignancies for which dedifferentiated liposarcoma is a plausible consideration after review of morphologic features. Clinicopathologic data, including patient age of diagnosis, tumor size, depth of tumor, results from MDM2 testing [when performed], anatomic location(s) and recurrence [where applicable], were collected for each patient. Results (if a Case Study enter NA) 1161 cases were assessed, 456 of whom underwent MDM2 testing, and 108 of which were ultimately classified as MDM2 amplified. Standardized bivariable comparisons found that a deep tumor location (p=0.0014) and older age (p=0.0002), but not tumor size at the >10 cm cut off were associated with MDM2 positivity. However, a logistic regression model showed that neither size, depth or age were significantly associated with MDM2 positivity. Among the MDM2-positive cohort, 91% had tumor sizes <10 cm, 14% were superficial, 23% were non-recurrent and 15% were less than the median cohort patient age of 58 years. If the aforementioned “traditional criteria” were used as the sole basis for MDM2 testing, 50 (46.29%) of the 108 cases that were ultimately classified as MDM2 positive would not have been tested. Conclusion Our findings suggest that a strict adherence to “traditional criteria” may result in a significant subset of MDM2 positive tumors not being tested in lipomatous tumors. A more expansive approach that incorporates additional indications for testing, should be evaluated.

BackgroundAdvances in treatment of peritoneal surface malignancies including cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS±HIPEC) have led to long-term survivorship, yet the subsequent quality of life (QOL) and values of these patients are unknown.Patients and MethodsSurvivors were offered surveys via online support groups. Novel items assessed how patients prioritized experience, costs, longevity, and wellbeing.ResultsOf the 453 gastrointestinal/hepatobiliary (GI/HPB) surgical patients that responded, 74 underwent CRS±HIPEC and were 54±12 years old, 87% female, and 93% white. Respondents averaged 29 months from diagnosis, with a maximum survival of 20 years. With a moderate level of agreement (W = 39%), rankings of value metrics among respondents were predictable (p < 0.001). Longevity and functional independence were ranked highest; treatment experience and cost of treatment were ranked lowest (p < 0.001). Those who underwent CRS±HIPEC or other GI/HPB surgeries reported the same rank order. QOL in CRS±HIPEC survivors, both mental (M-QOL) (44±13) and physical (P-QOL) (41±11) were lower than in the general population (50±10); p < 0.001. Impairments persisted throughout survivorship, but M-QOL improved over time (p < 0.05). When comparing CRS±HIPEC with other GI/HPB cancer surgery survivors, M-QOL (43±13 versus 43±14, p = 0.85) and P-QOL (40±11 versus 42±12, p = 0.41) were similar.ConclusionsAlthough CRS±HIPEC survivors experience long-term mental and physical health impairments, they were similar to those experienced by survivors of other GI/HPB cancer surgeries, and their QOL improved significantly throughout survivorship. As CRS±HIPEC survivors prioritize longevity above all other metrics, survival benefit may outweigh a temporary reduction in QOL.

Background Selected patients with peritoneal metastases of colorectal cancer (PM-CRC) can benefit from potentially curative cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC), with a median overall survival (OS) of more than 40 months. Objective The aims of this evidence-based consensus were to define the indications for HIPEC, to select the preferred HIPEC regimens, and to define research priorities regarding the use of HIPEC for PM-CRC. Methods The consensus steering committee elaborated and formulated pertinent clinical questions according to the PICO (patient, intervention, comparator, outcome) method and assessed the evidence according to the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) framework. Standardized evidence tables were presented to an international expert panel to reach a consensus (4-point, weak and strong positive/negative) on HIPEC regimens and research priorities through a two-round Delphi process. The consensus was defined as ≥ 50% agreement for the 4-point consensus grading or ≥ 70% for either of the two combinations. Results Evidence was weak or very weak for 9/10 clinical questions. In total, 70/90 eligible panelists replied to both Delphi rounds (78%), with a consensus for 10/10 questions on HIPEC regimens. There was strong negative consensus concerning the short duration, high-dose oxaliplatin (OX) protocol (55.7%), and a weak positive vote (53.8–64.3%) in favor of mitomycin-C (MMC)-based HIPEC (preferred choice: Dutch protocol: 35 mg/m 2 , 90 min, three fractions), both for primary cytoreduction and recurrence. Determining the role of HIPEC after CRS was considered the most important research question, regarded as essential by 85.7% of the panelists. Furthermore, over 90% of experts suggest performing HIPEC after primary and secondary CRS for recurrence > 1 year after the index surgery. Conclusions Based on the available evidence, despite the negative results of PRODIGE 7, HIPEC could be conditionally recommended to patients with PM-CRC after CRS. While more preclinical and clinical data are eagerly awaited to harmonize the procedure further, the MMC-based Dutch protocol remains the preferred regimen after primary and secondary CRS.

Chimeric antigen receptor T (CAR-T) cell therapy represents a major breakthrough in cancer treatment, and it has achieved unprecedented success in hematological malignancies, especially in relapsed/refractory (R/R) B cell malignancies. At present, CD19 and BCMA are the most common targets in CAR-T cell therapy, and numerous novel therapeutic targets are being explored. However, the adverse events related to CAR-T cell therapy might be serious or even life-threatening, such as cytokine release syndrome (CRS), CAR-T-cell-related encephalopathy syndrome (CRES), infections, cytopenia, and CRS-related coagulopathy. In addition, due to antigen escape, the limited CAR-T cell persistence, and immunosuppressive tumor microenvironment, a considerable proportion of patients relapse after CAR-T cell therapy. Thus, in this review, we focus on the progress and challenges of CAR-T cell therapy in hematological malignancies, such as attractive therapeutic targets, CAR-T related toxicities, and resistance to CAR-T cell therapy, and provide some practical recommendations.

Background No guidelines exist regarding the management of the uninvolved uterus or adnexa (fallopian tubes and/or ovaries) in patients with peritoneal metastases (PM) from non-gynecologic malignancies. It is unclear whether salpingo-oophorectomy, hysterectomy, or both should be performed when a complete pelvic peritonectomy is otherwise warranted. Methods A 25-item electronic survey was sent to 225 surgeons worldwide who routinely perform cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). Participants were recruited through listservs of expert groups. Individual surgeon approaches to the management of the grossly uninvolved uterus and adnexa in pre- and post-menopausal women with PM from low- and high-grade appendiceal neoplasms, colorectal cancer, and peritoneal mesothelioma were collected using a 5-point Likert scale. Results A total of 135 complete responses (60% response rate) were obtained from surgeons practicing in 27 countries. Respondents reported a median practice of 10 years (interquartile range [IQR] 6–15 years) and a median performance of 20 (IQR 12–30) CRS/HIPEC operations per year. Rates of salpingo-oophorectomy differed by histology and a woman’s menopausal status, ranging from 29 to 42% in pre-menopausal women to 71–77% in post-menopausal women ( P < 0.001). Notably, the number of surgeons who would perform a hysterectomy was lower, ranging from 12 to 27% for pre-menopausal women and from 32 to 44% for post-menopausal women, dependent on histology ( P < 0.001). Conclusions Surgeons are overall more aggressive with adnexal resection than with hysterectomy in both pre- and post-menopausal women with PM from non-gynecologic malignancies. Further prospective studies are required to determine the best approach to optimize surgical and oncologic outcomes while also accounting for the fertility and hormonal impact.

In this retrospective cohort study of 4671 inpatients with hematologic malignancies that required antibiotics, beta-lactam allergy label was associated with adverse clinical outcomes, specifically, increased hospital length of stay, mortality, total hospital charges, and complications. Abstract Background Patients hospitalized with hematologic malignancy are particularly vulnerable to infection. The impact of reported beta-lactam (BL) allergy in this population remains unknown. Methods This was a retrospective cohort study of adult inpatients with hematologic malignancy admitted at 2 tertiary care hospitals from 2010 through 2015. The primary outcome was hospital length of stay (LOS) after administration of the first antibiotic. Secondary outcomes included readmission, mortality, complications, hospital charges, and antibiotic usage. Our goal was to define the impact of BL-only allergy (BLOA) label on clinical outcomes compared to those with no BL allergy (NBLA) in hematologic malignancy inpatients who required systemic antibiotics. Results In our cohort (n = 4671), 38.3% had leukemia, 4.9% had Hodgkin lymphoma, 36.1% had non-Hodgkin lymphoma, and 20.7% had multiple myeloma. Among patients, 35.1% reported antibiotic allergy, and 14.1% (n = 660) had BLOA (including 9.3% with penicillin-only allergy and 3.3% cephalosporin-only allergy). Patients with BLOA had longer median LOS compared to patients with NBLA (11.3 vs 7.6 days, P < .001), which remained significant after multivariable adjustment. Patients with BLOA also had significantly worse outcomes in terms of mortality rate at 30 days (7.6% vs 5.3%, P = .017) and 180 days (15.8% vs 12.2%, P = .013), 30-day readmission rate, Clostridium difficile rate, hospital charges ($223 046 vs $173 256, P < .001), antibiotic classes used, and antibiotic duration. Conclusions In hospitalized patients with hematologic malignancy, patients with reported BL allergy had worse clinical outcomes and higher healthcare cost than those without BL allergy label.