Evaluation of the efficacy and safety of immunotherapy in sarcoma: a two-center study
Zhichao LiaoJianjin TengTao LiHaotian LiuTing LiChao ZhangRuwei XingSheng TengYun YangJun ZhaoWanyi XiaoGengpu ZhangMulin Jun LiWeitao YaoJilong Yang
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Background Sarcoma is a highly heterogeneous malignancy with a poor prognosis. Although chemotherapy and targeted therapy have improved the prognosis to some extent, the efficacy remains unsatisfactory in some patients. The efficacy and safety of immunotherapy in sarcoma need further evaluation. Methods We conducted a two-center study of sarcoma patients receiving PD-1 immunotherapy at Tianjin Medical University Cancer Institute and Hospital and Henan Provincial Cancer Hospital. The treatment regimens included PD-1 inhibitor monotherapy and combination therapy based on PD-1 inhibitors. The observed primary endpoints were median progression-free survival (mPFS) and median overall survival (mOS). Survival curves were compared using the Kaplan−Meier method. Results A total of 43 patients were included from the two centers. The median follow-up time for all patients was 13 months (range, 1-48 months). In the group of 37 patients with advanced or unresectable sarcoma, the mPFS was 6 months (95%CI: 5-12 months), and the mOS was 16 months (95%CI: 10-28 months). The ORR was 10.8% (4/37), and the DCR was 18.9% (7/37). Subgroup analysis showed no significant differences in mPFS (p=0.11) and mOS (p=0.88) between patients with PD-L1 negative/positive expression. There were also no significant differences in mPFS (p=0.13) or mOS (p=0.72) between PD-1 inhibitor monotherapy and combination therapy. Additionally, there were no significant differences in mPFS (p=0.52) or mOS (p=0.49) between osteogenic sarcoma and soft tissue sarcoma. Furthermore, the results showed no significant differences in mPFS (p=0.66) or mOS (p=0.96) between PD-1 inhibitors combined with targeted therapy and PD-1 inhibitors combined with AI chemotherapy. Among the 6 patients receiving adjuvant therapy after surgery, the mPFS was 15 months (95%CI: 6-NA months), and the mOS was not reached. In terms of safety, most adverse events were mild (grade 1-2) and manageable. The most severe grade 4 adverse events were bone marrow suppression, which occurred in 4 patients but resolved after treatment. There was also one case of a grade 4 adverse event related to hypertension. Conclusion Immunotherapy is an effective treatment modality for sarcoma with manageable safety. Further inclusion of more patients or prospective clinical trials is needed to validate these findings.Keywords:
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CHOP chemotherapy has been used as a standard first-line treatment for diffuse large B-cell lymphoma since the 1970s. Phase III trials have shown that the addition of rituximab (R) to CHOP chemotherapy leads to significant improvements in response rate, progression-free survival and overall survival. This single-center, retrospective study was performed to evaluate the role of the addition of R to chemotherapy (CHT) in a real-world clinical setting. Outcomes were assessed in 85 patients with newly diagnosed DLBCL treated with CHT alone (n=38) and R-CHT (n=47). Complete response (CR) rates were significantly higher after R-CHT than CHT (93 % vs. 73 %; p=0.02). The relapse rate was significantly higher after CHT compared with R-CHT (38 % versus 12 %; p=0.01). Progression-free survival was significantly extended by the addition of R (median not reached versus 26.1 months; p=0.04). These data bring further support for rituximab- based immunochemotherapy as a standard first-line therapy for patients with DLBCL.
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During the limb preserving procedure for musculoskeletal sarcoma, the course of action that should be taken when a tumor or tumor-cell-contaminated adjacent tissue is violated remains controversial. From January, 1973, to July, 1989, 120 patients with musculoskeletal sarcoma were treated by limb salvage surgery and, in 40 of them, such violations inadvertently occurred during surgery. Follow-up studies on the patients have been conducted for at least one year after the violation. Soft tissue sarcoma was noted in 24 cases (low grade, 4; high grade, 20) and bone sarcoma in 16 (low grade, 6; high grade, 10). To treat the violation, re-excision with a clean margin and copious lavage was generally conducted after careful closure of the violated site. Sixteen cases in the soft tissue sarcoma group and eight in the bone sarcoma group were treated in this way. Local recurrences were found in 13 of the 40 cases (33%), but the percentage was reduced to 13 in cases treated by re-excision with a clean margin. In the present study, there was no significant effect of adjuvant therapy after violation. The survival rate in cases of local recurrence was very low, and not at all improved by adjuvant therapy.
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Ewing’s sarcoma is a common pediatric sarcoma. There is a subset of tumors similar to Ewing’s sarcoma in several aspects, but negative for all known translocations. The BCOR sarcoma is one example. There are limited descriptions of the radiologic imaging findings. Previous reports describe the radiologic features as “aggressive” and “similar” to Ewing’s sarcoma. This implies a permeative lesion centered in the diaphysis. Our case was geographic with a well-defined border and sharp zone of transition. Keywords: Ewing’s sarcoma, BCOR sarcoma, Imaging.
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The Australia and New Zealand Sarcoma Association established the Sarcoma Guidelines Working Party to develop national guidelines for the management of Sarcoma. We asked whether surgery at a specialised centre improves outcomes. A systematic review was performed of all available evidence pertaining to paediatric or adult patients treated for bone or soft tissue sarcoma at a specialised centre compared with non-specialised centres. Outcomes assessed included local control, limb salvage rate, 30-day and 90-day surgical mortality, and overall survival. Definitive surgical management at a specialised sarcoma centre improves local control as defined by margin negative surgery, local or locoregional recurrence, and local recurrence free survival. Limb conservation rates are higher at specialised centres, due in part to the depth of surgical experience and immediate availability of multidisciplinary and multimodal therapy. A statistically significant correlation did not exist for 30-day and 90-day mortality between specialised centres and non-specialised centres. The literature is consistent with improved survival when definitive surgical treatment is performed at a specialised sarcoma centre. Evidence-based recommendation: Patients with suspected sarcoma to be referred to a specialised sarcoma centre for surgical management to reduce the risk of local recurrence, surgical complication, and to improve limb conservation and survival. Practice point: Patients with suspected sarcoma should be referred to a specialised sarcoma centre early for management including planned biopsy.
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Objective: To identify factors influencing the survival of liver transplanted patients with Model-for-End-Stage-Liver-Disease (MELD)-Score of 40. Summary Background Data:Organ shortage and the related waiting-list mortality have led to changes in the allocation criteria and introduction of the MELD-Score in the Eurotransplant Era. The highest medical urgency represents the current allocation principle for liver transplantation (LT). Patients with MELD-Score 40 have a 3-month survival probability of almost 0% without LT. Patients and Methods: Data of all adult patients transplanted in a 3.5-year period with a labMELD-score 40 were reviewed. Recipients with acute liver failure, high urgency listed patients for re-transplantation or patients receiving live donor LT were excluded. All operations were performed using standard surgical techniques. Donor and recipient perioperative characteristics, operative details, treatment-related complications and pathological findings were analyzed. Statistical analysis encompassed Kaplan-Meier analysis/log-rank test as well as univariate and multivariable Cox proportional hazard regression analyses. Results: Thirty patients were considered. The survival rate regarding the first 3, 6 and 9 months was 53% respectively and 50% after one year. 3-year patient survival was 50%. A re-transplantation has been performed in 4 cases. Graft survival was 57% at 3, 6, and 9 months, and 53% at one year, respectively. Forty-three variables were evaluated for prognostic significance. Multivariable analysis revealed preoperative dialysis (p=0.0246) and portal vein thrombosis (PVT) (p=0.0231) to be independent prognostic factors for patient survival. A point scoring system was determined as follows: patients without PVT: patients with PVT=0:1 points; patients without pre-LT dialysis: patients with pre-LT dialysis=0:1 points. The model reached statistical significance (p=0.0007). 3-, and 12-months survival for scores 0, 1 and 2 were 72% and 72%, 51% and 42%, and 0%, respectively. Conclusions: According to our study coexistence of preoperative dialysis and PVT represents a clear contraindication for LT regarding MELD-score 40 patients.
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Kaposi's sarcoma is the leading cancer in much of sub-Saharan Africa [1]. HIV has resulted in a dramatic increase in Kaposi's sarcoma throughout the region due to high overlapping prevalence of HIV and the etiologic agent of Kaposi's sarcoma, Kaposi's sarcoma–associated herpesvirus (KSHV) [2]. Kaposi's sarcoma is divided into four major categories: classical, iatrogenic, AIDS-related, and endemic. Endemic Kaposi's sarcoma is the only Kaposi's sarcoma subtype in which a specific immune disturbance is not readily apparent [3]. In Malawi, Kaposi's sarcoma is the leading cancer overall accounting for 34% of all malignancies recorded in the national cancer registry [4]. In a setting of high Kaposi's sarcoma burden, we sought to describe contemporary burden and characteristics of Kaposi's sarcoma in the HIV-positive and HIV-negative populations at a national teaching hospital in the capital, Lilongwe. We analyzed Kaposi's sarcoma cases from May 2014 until May 2016 in the Kamuzu Central Hospital Cancer Registry, which involves active registration of cancer cases across all hospital departments using standardized data collection forms. We identified 237 overall Kaposi's sarcoma cases, of which 153 were confirmed HIV-positive and 21 confirmed HIV-negative. Kaposi's sarcoma diagnoses were histologically confirmed in 39% (92/237) of cases overall, including 33% (50/153) of confirmed HIV-positive and 71% (15/21) of confirmed HIV-negative cases. We abstracted tumor location and subtype from all confirmed histology reports. As expected, Kaposi's sarcoma patients were more commonly men regardless of HIV status (Table 1). Age distribution was significantly different based on HIV status [P = 0.012, Fisher's exact test, Figure, Supplemental Digital Content 1, https://links.lww.com/QAD/B18; graph of Kaposi's sarcoma age distribution within HIV+ and HIV− by decade]. HIV-positive cases primarily presented during young-to-mid-adulthood with 68% of cases occurring between 20 and 49 years of age. By contrast, HIV-negative cases were more evenly distributed among age groups. HIV-positive Kaposi's sarcoma tended to present with disease at diverse anatomical sites, whereas HIV-negative Kaposi's sarcoma appeared to primarily present in the lower extremities (60%). Similarly, lesion descriptions in pathology reports suggested greater lesion heterogeneity among HIV-positive patients, with predominantly plaque or nodular lesions among HIV-negative patients (73%). Finally, among patients for whom the primary treatment modality was recorded, 49% of HIV-positive patients and 33% of HIV-negative patients received chemotherapy. Of note, radiotherapy is not available in Malawi.Table 1: Kaposi's sarcoma demographics at Kamuzu Central Hospital.These findings suggest that, despite a high HIV prevalence in Malawi, HIV-negative endemic Kaposi's sarcoma represents at least 9% of contemporary Kaposi's sarcoma burden at a national teaching hospital, with possible differences in presenting characteristics between HIV-positive and HIV-negative patients. Despite major investments and research programs in the region focused on AIDS-related Kaposi's sarcoma, endemic Kaposi's sarcoma has received relatively little attention. At our center, endemic Kaposi's sarcoma appeared to occur at both younger and older ages compared with HIV-positive Kaposi's sarcoma. Lifelong KSHV infection in sub-Saharan Africa is often acquired in childhood through salivary and breast milk transmission, although KSHV may also be acquired in adulthood. Subsequent infection with HIV during adulthood abruptly alters host immune function allowing Kaposi's sarcoma development, accounting for high Kaposi's sarcoma burden in the HIV-positive population between ages 20 and 49 years. In the absence of HIV, precipitating cofactors of endemic Kaposi's sarcoma remain unclear and may be associated with volcanic soils, African natural products, and genetic predisposition [5–7]. As antiretroviral therapy (ART) scale-up continues in Malawi, which began in 2004, with ART coverage now reaching 67% of eligible HIV-positive patients [8], the incidence of AIDS-associated Kaposi's sarcoma is anticipated to decline. These trends, coupled with demographic shifts in sub-Saharan Africa with aging of populations overall, may result in higher proportions of Kaposi's sarcoma in older individuals and relatively constant burden among children, regardless of HIV status. At our center, many of these patients had severe enough disease to require treatment with chemotherapy at a tertiary referral oncology clinic. This may become increasingly important as treatment of older patients with cytotoxic therapy is challenging in resource-limited settings without appropriate supportive care infrastructure. Novel treatment paradigms, including greater application of noncytotoxic therapies and local treatments for limited-stage disease, may therefore be needed. Finally, questions remain as to how endemic Kaposi's sarcoma evolves from KSHV infection. Studies in the United States and Malawi suggest the presence of at least two subtypes of Kaposi's sarcoma on the basis of gene expression profiling [9,10]. Understanding precipitating and viral factors in HIV-negative populations may help guide therapy development and prevention efforts. In conclusion, embedded efforts to better understand endemic Kaposi's sarcoma are needed within larger regional initiatives focused on AIDS-related Kaposi's sarcoma. If successful, such efforts have the potential to guide prevention and treatment strategies, which can better address overall Kaposi's sarcoma burden in Malawi and comparable settings, as ART scale-up continues and populations continue to age. Acknowledgements K.M.H. performed primary data analysis and manuscript preparation. M.-J.H. contributed to establishing the cancer registry and data acquisition. T.v.d.G. performed all statistical analysis. A.M., S.P., and S.G. treated patients included in the study. D.P.D., B.D., and S.G. provided funds for both the cancer registry and the study performed. All authors contributed to manuscript preparation via helpful discussions and text edits. NIH grants CA019014, CA190152, CA192744, CA210285, DE018281, CA163217, U54CA190152, P30CA016086, and 5T32AI007419-23 and the MEPI grant U2GPS001965. S.G., A.M., and D.P.D. are investigators of the AIDS malignancies consortium (2UM1CA121947). B.D. is a Leukemia and Lymphoma Society Scholar and a Burroughs Wellcome Fund Investigator in Infectious Disease. K.M.H. also received funding from a University of North Carolina global health award. Conflicts of interest There are no conflicts of interest.
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Ewing’s sarcoma is a common pediatric sarcoma. There is a subset of tumors similar to Ewing’s sarcoma in several aspects, but negative for all known translocations. The BCOR sarcoma is one example. There are limited descriptions of the radiologic imaging findings. Previous reports describe the radiologic features as “aggressive” and “similar” to Ewing’s sarcoma. This implies a permeative lesion centered in the diaphysis. Our case was geographic with a well-defined border and sharp zone of transition. Keywords: Ewing’s sarcoma, BCOR sarcoma, Imaging
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