Soft tissue sarcomas are a heterogeneous and rare group of solid tumors of mesenchymal origin that can arise anywhere in the body. Although surgical resection is the mainstay of treatment for ...patients with localized disease, disease recurrence is common and 5-year overall survival is poor (~ 65%). Both radiation therapy and conventional chemotherapy are used to reduce local and distant recurrence. However, the utility of radiation therapy is often limited by disease location (in the case of retroperitoneal sarcomas, for instance) while systemic therapy with conventional lines of chemotherapy offer limited efficacy and are often poorly tolerated and associated with significant toxicity. Within the past decade, major advances have been made in the treatment of other malignancies including melanoma, renal cell carcinoma, and non-small cell lung carcinoma with the advent of immune-checkpoint inhibitors such as ipilimumab (anti-CTLA4), pembrolizumab (anti-PD1), and nivolumab (anti-PD1). The recently published SARC028 (NCT02301039), an open label, phase II, multicenter trial of pembrolizumab in patients with advanced bone and soft tissue sarcomas reported promising activity in select histologic subtypes of advanced STS, including undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma.
There is a clear need for novel and effective adjuncts in the treatment of STS. We hypothesize that immune checkpoint blockade will be effective in patients with surgically resectable primary or locally recurrent dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma when administered in the neoadjuvant setting. The primary aim of this phase II, single-center, open label, randomized non-comparative trial is to determine the pathologic response to neoadjuvant nivolumab monotherapy and combination nivolumab/ipilimumab in patients with resectable dedifferentiated liposarcoma of the retroperitoneum or undifferentiated pleomorphic sarcoma of the trunk or extremity treated with concurrent standard of care neoadjuvant radiation therapy.
This study will help define the role of single agent anti-PD1 and combination anti-CTLA4 and anti-PD1 therapy in patients with surgically resectable dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma.
ClinicalTrials.gov NCT03307616 , registered October 12, 2017.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVE Malignant peripheral nerve sheath tumors (MPNSTs) are an aggressive group of soft tissue sarcomas that can arise sporadically, in the context of neurofibromatosis Type 1 (NF1) or at a site ...of prior irradiation. Large series profiling the features and outcomes of sporadic, NF1-associated, and radiation-associated MPNSTs are limited. The goal of this study was to elucidate differences between MPNST etiologies in a large single-institution retrospective study. METHODS Patients (n = 317) were identified through the tumor registry of The University of Texas MD Anderson Cancer Center. Clinicopathological features were retrospectively collected. Features were compared among MPNST subtypes for patients who had sufficient clinical history (n = 289), and clinicopathological features were used to identify adverse predictors of recurrence and survival outcomes. RESULTS Five-year local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), and disease-specific survival (DSS) estimates were 56.6%, 49.6%, and 53.6%, respectively, for the high-grade MPNST cohort. Five-year DSS was lower in NF1-associated and radiation-associated MPNST than in sporadic MPNST (52%, 47%, and 67%, respectively, p = 0.140). Patients with radiation-associated MPNST had worse 5-year LRFS than those with the sporadic and NF1-associated subtypes (RT-associated vs sporadic, p = 0.010; RT-associated vs NF1-associated, p = 0.232). Truncally located tumors, positive surgical margins, local recurrence, and metastasis were predictors of adverse DSS in multivariate analysis. CONCLUSIONS Radiation-associated MPNSTs are associated with poorer local recurrence-free and disease-specific survival than sporadic and NF1-associated tumors. NF1-associated MPNSTs may have worse survival outcomes owing to large tumor size, compromising truncal location, and lower rate of negative resection margins compared with sporadic tumors.
Our goal was to evaluate use and associated costs of radiation therapy (RT) in the last month of life among those dying of cancer.
We used the Surveillance, Epidemiology, and End Results (SEER) ...-Medicare linked databases to analyze claims data for 202,299 patients dying as a result of lung, breast, prostate, colorectal, and pancreas cancers from 2000 to 2007. Logistic regression modeling was used to conduct adjusted analyses of potential impacts of demographic, health services, and treatment-related variables on receipt of RT and treatment with greater than 10 days of RT. Costs were calculated in 2009 dollars.
Among the 15,287 patients (7.6%) who received RT in the last month of life, its use was associated with nonclinical factors such as race, gender, income, and hospice care. Of these patients, 2,721 (17.8%) received more than 10 days of treatment. Nonclinical factors that were associated with greater likelihood of receiving more than 10 days of RT in the last 30 days of life included: non-Hispanic white race, no receipt of hospice care, and treatment in a freestanding, versus a hospital-associated facility. Hospice care was associated with 32% decrease in total costs of care in the last month of life among those receiving RT.
Although utilization of RT overall was low, almost one in five of patients who received RT in their final 30 days of life spent more than 10 of those days receiving treatment. More research is needed into physician decision making regarding use of RT for patients with end-stage cancer.
In the last few years there have been dramatic changes in the management of patients with melanoma with locally advanced disease. Previously, standard therapy for melanoma patients with nodal disease ...involved completion lymph node dissection followed by adjuvant radiation therapy for high-risk features, as defined by TROG 02.01. Adjuvant systemic therapy with interferon could be offered, but many eligible patients did not receive this agent in the context of significant toxicity. New, effective, and often well-tolerated systemic therapies, such as immune checkpoint inhibitors and targeted MAPK pathway inhibitors, have shown impressive responses in metastatic disease and are now being applied to the locally advanced setting. Currently, for patients with occult nodal disease found at sentinel lymph node biopsy, completion lymph node dissection is uncommon with adjuvant anti-PD1 therapy often recommended. For patients with clinically apparent nodal disease, neoadjuvant immunotherapy has shown impressive pathologic response rates, which thus far have correlated well with longer term disease outcomes. However, not all patients exhibit a robust pathologic response. In circumstances of either occult nodal disease or clinically evident nodal disease without a robust pathologic response to neoadjuvant immunotherapy, there is a dearth of evidence regarding the optimal use of radiation therapy. Prospective studies investigating the role of adjuvant nodal radiation therapy for melanoma patients in the modern immunotherapy era are much needed.
Geographic access to care may be associated with receipt of chemotherapy but has not been fully examined. This study sought to evaluate the association between density of oncologists and travel ...distance and receipt of adjuvant chemotherapy for colon cancer within 90 days of colectomy.
Patients in the National Cancer Data Base with stage III colon cancer, diagnosed between 2007 and 2010, and age 18 to 80 years were selected. Generalized estimating equation clustering by hospital service area was conducted to examine the association between geographic access and receipt of oncology services, controlling for patient sociodemographic and clinical characteristics.
Of 34,694 patients in the study cohort, 75.7% received adjuvant chemotherapy within 90 days of colectomy. Compared with travel distance less than 12.5 miles, patients who traveled 50 to 249 miles (odds ratio OR, 0.87; P=.009) or ≥250 miles (OR, 0.36; P<.001) had decreased likelihood of receiving adjuvant chemotherapy. Density level of oncologists was not statistically associated with receipt of adjuvant chemotherapy (low v high density: OR, 0.98; P=.77). When stratifying analyses by insurance status, non-privately insured patients who resided in areas with low density of oncologists were less likely to receive adjuvant chemotherapy (OR, 0.85; P=.03).
Increased travel burden was associated with a decreased likelihood of receiving adjuvant chemotherapy, regardless of insurance status. Patients with nonprivate insurance who resided in low-density oncologist areas were less likely to receive adjuvant chemotherapy. If these findings are validated prospectively, interventions to decrease geographic barriers may improve the timeliness and quality of colon cancer treatment.
The purpose of this study was to determine the association of insurance status with disease stage at presentation, treatment, and survival among the top 10 most deadly cancers using the SEER ...database.
A total of 473,722 patients age 18 to 64 years who were diagnosed with one of the 10 most deadly cancers in the SEER database from 2007 to 2010 were analyzed. A Cox proportional hazards model was used for multivariable analyses to assess the effect of patient and tumor characteristics on cause-specific death.
Overall, patients with non-Medicaid insurance were less likely to present with distant disease (16.9%) than those with Medicaid coverage (29.1%) or without insurance coverage (34.7%; P < .001). Patients with non-Medicaid insurance were more likely to receive cancer-directed surgery and/or radiation therapy (79.6%) compared with those with Medicaid coverage (67.9%) or without insurance coverage (62.1%; P < .001). In a Cox regression that adjusted for age, race, sex, marital status, residence, percent of county below federal poverty level, site, stage, and receipt of cancer-directed surgery and/or radiation therapy, patients were more likely to die as a result of their disease if they had Medicaid coverage (hazard ratio HR, 1.44; 95% CI, 1.41 to 1.47; P < .001) or no insurance (HR, 1.47; 95% CI, 1.42 to 1.51; P < .001) compared with non-Medicaid insurance.
Among patients with the 10 most deadly cancers, those with Medicaid coverage or without insurance were more likely to present with advanced disease, were less likely to receive cancer-directed surgery and/or radiation therapy, and experienced worse survival.
Low socioeconomic and health care access realities of being American Indian/Alaskan Native (AI/AN) in the United States combined with decades of data documenting poor cancer outcomes for this ...population provide a population nested within the United States that is analogous to the cancer care landscape of low- and middle-income countries internationally. We reviewed the medical literature with respect to cancer prevention, access to cancer treatment, and access to effective supportive and palliative care for AI/AN populations in the United States. Research confirms poorer cancer outcomes, suboptimal cancer screening, and high-risk cancer behaviors among AI/AN communities. AI/AN cancer patients are less likely to undergo recommended cancer surgeries, adjuvant chemotherapy, and radiation therapy than their White counterparts. Studies including both rural and urban survivors with AI cancer revealed barriers to receipt of optimal cancer symptom management and proportionally lower hospice use among AI/AN populations. Culturally tailored programs in targeted communities have been shown to mitigate the observed cancer-related health disparities among AI/AN communities. There is still much work to be done to improve cancer-related health outcomes in AI/AN communities, and the goals of the providers serving them corresponds with those propelling the growing interest in global oncology equity. Policy work and more funding are needed to continue to build upon the work that the Indian Health Service and established cancer-related health programs have begun in AI/AN communities.
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