Search

Purpose: It is unclear how NCCN guidelines recommend "supportive care" and "best supportive care" in oncology practice. We examined the usage of "supportive care" and "best supportive care" in NCCN guidelines and compared between solid tumor and hematologic malignancy guidelines. Methods: We reviewed all updated NCCN Guidelines for Treatment of Cancer in October 2019. We documented the frequency of occurrence, definition, and timing of introduction of each term. We compared between solid tumor and hematologic malignancy guidelines. Results: We identified a total of 37 solid tumor and 16 hematologic guidelines. Thirty-seven (70%) guidelines mentioned "supportive care" and 36 (68%) mentioned "best supportive care." Hematologic guidelines were significantly more likely than solid tumor guidelines to use the term "supportive care" (median occurrence 19 vs. 2; P = 0.001) and to describe "supportive care" as management of cancer-related complications (N = 11/15, 73% vs. N = 2/22, 9%; P < 0.001). Domains of specialist palliative care were infrequently mentioned (N = 10/37, 27%). In contrast, solid tumor guidelines were significantly more likely than hematologic guidelines to mention "best supportive care" (median occurrence 6 vs. 0; P = 0.016). This term was rarely defined and mostly used in the advanced disease setting. Conclusion: "Supportive care" and "best supportive care" were frequently used in NCCN guidelines, with significant variations in usage between solid tumor and hematologic oncologists. "Supportive care" was mostly limited to management of cancer-related complications and treatment adverse effects in NCCN guidelines, highlighting the need to go beyond the traditional biomedical model to more a patient-centered care model with greater integration of palliative care. [ABSTRACT FROM AUTHOR]

A large number of surveys have been sent to the medical physics community addressing many clinical topics for which the medical physicist is, or may be, responsible. Each survey provides an insight into clinical practice relevant to the medical physics community. The goal of this study was to create a summary of these surveys giving a snapshot of clinical practice patterns. Surveys used in this study were created using SurveyMonkey and distributed between February 6, 2013 and January 2, 2018 via the MEDPHYS and MEDDOS listserv groups. The format of the surveys included questions that were multiple choice and free response. Surveys were included in this analysis if they met the following criteria: more than 20 responses, relevant to radiation therapy physics practice, not single‐vendor specific, and formatted as multiple‐choice questions (i.e., not exclusively free‐text responses). Although the results of free response questions were not explicitly reported, they were carefully reviewed, and the responses were considered in the discussion of each topic. Two‐hundred and fifty‐two surveys were available, of which 139 passed the inclusion criteria. The mean number of questions per survey was 4. The mean number of respondents per survey was 63. Summaries were made for the following topics: simulation, treatment planning, electron treatments, linac commissioning and quality assurance, setup and treatment verification, IMRT and VMAT treatments, SRS/SBRT, breast treatments, prostate treatments, brachytherapy, TBI, facial lesion treatments, clinical workflow, and after‐hours/emergent treatments. We have provided a coherent overview of medical physics practice according to surveys conducted over the last 5 yr, which will be instructive for medical physicists. [ABSTRACT FROM AUTHOR]

Background: The majority of women with endometrial cancer (EC) present at an early stage with an associated 5-year survival rate of >90%. High rates of early detection are attributed to warning symptoms; however, the prevalence of such symptoms has not been well defined. Methods: A case-control study was conducted assessing the prevalence of symptoms in EC patients at a large cancer center compared with healthy controls. Controls included patients seen for an annual gynecologic care visit (AV) or for a gynecological problem-based visit (PV). A self-administered questionnaire was given to all participants addressing EC-associated symptoms, at the time of initial clinic visit. Odds ratios (ORs) were used to compare prevalence of symptoms between EC cases and controls. Logistic regression was used to determine the impact of menopausal status and obesity on symptom prevalence. Results: The cases ( n = 75) were significantly older than the AV ( n = 203) and PV ( n = 151) controls (59.7 vs. 49.8 vs. 51.0 years, p < 0.01), had a higher body mass index (35.5 vs. 29.4 vs. 30.9 kg/m2, p < 0.01), and were more likely to be postmenopausal (76% vs. 53.7% vs. 52.0%, p < 0.01). The cases were more likely to report postmenopausal bleeding (OR = 32.99 and 5.83, p < 0.01) and abnormal vaginal discharge (OR = 8.8 and 3.3, p < 0.01) compared with the AV and PV groups. Overall, 55.4% of cases reported abnormal vaginal discharge. Conclusions: Symptoms of both postmenopausal bleeding and abnormal vaginal discharge were significantly higher in EC compared with controls. The presence of such symptoms should raise concern for malignant disease and prompt immediate gynecological evaluation. [ABSTRACT FROM AUTHOR]

Objective To evaluate how many patients could have undergone partial nephrectomy ( PN) rather than radical nephrectomy ( RN) before and after neoadjuvant axitinib therapy, as assessed by five independent urological oncologists, and to study the variability of inter-observer agreement. Patients and Methods Pre- and post-systemic treatment computed tomography scans from 22 patients with clear cell renal cell carcinoma in a phase II neoadjuvant axitinib trial were reviewed by five independent urological oncologists. R.E.N.A.L. nephrometry score and κ statistics were calculated. Results The median R.E.N.A.L. nephrometry score changed from 11 before treatment to 10 after treatment ( P = 0.002). Five tumours with moderate complexity before axitinib treatment remained moderate complexity after treatment. Of 17 tumours with high complexity before axitinib treatment, three became moderate complexity after treatment. The overall κ statistic was 0.611. Moderate-complexity κ was 0.611 vs a high-complexity κ of 0.428. Before axitinib treatment the κ was 0.550 vs 0.609 after treatment. After treatment with axitinib, all five reviewers agreed that only five patients required RN (instead of eight before treatment) and that 10 patients could now undergo PN (instead of three before treatment). The odds of PN feasibility were 22.8-times higher after treatment with axitinib. Conclusions There is considerable variability in inter-observer agreement on the feasibility of PN in patients treated with neoadjuvant targeted therapy. Although more patients were candidates for PN after neoadjuvant axitinib therapy, it remains difficult to identify these patients a priori. [ABSTRACT FROM AUTHOR]

Objective: To assess efficacy of the levonorgestrel-releasing intrauterine device (LNG-IUD) for treatment of complex atypical hyperplasia or low-grade endometrial cancer.Methods: This retrospective case series included all patients treated with the LNG-IUD for complex atypical hyperplasia or early-grade endometrial cancer from January 2003 to June 2013. Response rates were calculated and the association of response with clinicopathologic factors, including age, body mass index, and uterine size, was determined.Results: Forty-six patients diagnosed with complex atypical hyperplasia or early-grade endometrial cancer were treated with the LNG-IUD. Of 32 evaluable patients at the 6-month time point, 15 had complex atypical hyperplasia (47%), nine had G1 endometrial cancer (28%), and eight had grade 2 endometrial cancer (25%). Overall response rate was 75% (95% CI 57-89) at 6 months; 80% (95% CI 52-96) in complex atypical hyperplasia, 67% (95% CI 30-93) in grade 1 endometrial cancer, and 75% (CI 35-97) in grade 2 endometrial cancer. Of the clinicopathologic features evaluated, there was a trend toward the association of lack of exogenous progesterone effect in the pathology specimen with nonresponse to the IUD (P=.05). Median uterine diameter was 1.3 cm larger in women who did not respond to the IUD (P=.04).Conclusion: Levonorgestrel-releasing IUD therapy for the conservative treatment of complex atypical hyperplasia or early-grade endometrial cancer resulted in return to normal histology in a majority of patients. [ABSTRACT FROM AUTHOR]

Background Previous studies have shown a modest impact of tyrosine kinase inhibitors on primary renal tumors. Those studies were mostly retrospective or heterogeneous in their eligibility criteria with regard to histology, disease stage, duration of therapy, and time off therapy prior to surgery. Objective To prospectively investigate the safety and efficacy of axitinib in downsizing tumors in patients with nonmetastatic biopsy-proven clear cell renal cell carcinoma (ccRCC). Design, setting, and participants This was a single-institution, single-arm phase 2 clinical trial. Patients with locally advanced nonmetastatic biopsy-proven ccRCC were eligible. Intervention Patients received axitinib 5 mg for up to 12 wk. Axitinib was continued until 36 h prior to surgery. Patients underwent partial or radical nephrectomy after axitinib therapy. Outcome measurements and statistical analysis The primary outcome was objective response rate prior to surgery. Secondary outcomes included safety, tolerability, and quality of life. A dedicated radiologist independently reviewed all computed tomography scans to evaluate for response using Response Evaluation Criteria in Solid Tumors (RECIST). Results and limitations A total of 24 patients were treated. Twenty-two patients continued axitinib for 12 wk; 1 patient continued axitinib for 11 wk and underwent surgery as planned. One patient stopped treatment at 7 wk due to adverse events (AEs). Median reduction of primary renal tumor diameter was 28.3%. Eleven patients experienced a partial response per RECIST; 13 had stable disease. There was no progression of disease while on axitinib. The most common AEs were hypertension, fatigue, oral mucositis, hypothyroidism, and hand-foot syndrome. Postoperatively, 2 grade 3 and 13 grade 2 complications were noted. No grade 4 or 5 complications occurred. Functional Assessment of Cancer Therapy-Kidney Specific Index-15 changed over time, with quality of life worsening while on therapy, but by week 19, it was not statistically different from screening. Limitations include single-arm design and small patient numbers. Conclusions Axitinib was clinically active and reasonably well tolerated in the neoadjuvant setting in patients with locally advanced nonmetastatic ccRCC. Patient summary In this prospective clinical trial, we found that axitinib, when given prior to surgery, results in significant shrinking of kidney cancers. Larger studies are needed prior to further clinical use. Trial registration This clinical trial was registered with clinicaltrials.gov ( NCT01263769 ). [ABSTRACT FROM AUTHOR]

Our pilot clinical study of EphA2 inhibitor (dasatinib) plus paclitaxel and carboplatin showed interesting clinical activity in endometrial cancer with manageable toxicity. However, the underlying mechanisms of dasatinib resistance in uterine cancer are unknown. Here, we investigated potential mechanisms underlying resistance to EphA2 inhibitors in uterine cancer and examined the anti-tumor activity of EphA2 inhibitors alone and in combination with a MEK inhibitor. We evaluated the antitumor activity of EphA2 inhibitors plus a MEK inhibitor using in vitro and in vivo orthotopic models of uterine cancer. EphA2 inhibitor induced MAPK in dasatinib-resistant uterine cancer cells (HEC-1A and Ishikawa) and BRAF/CRAF heterodimerization in HEC-1A cells. EphA2 inhibitor and trametinib significantly increased apoptosis in cancer cells resistant to EphA2 inhibitors compared with controls (p < 0.01). An in vivo study with the orthotopic HEC-1A model showed significantly greater antitumor response to combination treatment compared with dasatinib alone (p < 0.01). Combination treatment increased EphrinA1 and BIM along with decreased pMAPK, Jagged 1, and c-MYC expression in dasatinib-resistant cells. In addition, Spearman analysis using the TCGA data revealed that upregulation of EphA2 was significantly correlated with JAG1, MYC , NOTCH1 , NOTCH3 and HES1 expression (p < 0.001, r = 0.25–0.43). Specifically, MAP3K15 and the NOTCH family genes were significantly related to poor clinical outcome in patients with uterine cancer. These findings indicate that the MAPK pathway is activated in dasatinib-resistant uterine cancer cells and that EphrinA1-mediated MEK inhibition overcomes dasatinib resistance. Dual targeting of both EphA2 and MEK, combined with chemotherapy, should be considered for future clinical development. • Our pilot clinical study of dasatinib showed clinical activity in endometrial cancer. • The underlying mechanisms of dasatinib resistance in uterine cancer are unknown. • MAPK pathway is activated in dasatinib-resistant uterine cancer cells. • MEK inhibition overcomes dasatinib resistance in uterine cancer. • Dual targeting of EphA2 and MEK should be considered for future clinical development. [ABSTRACT FROM AUTHOR]

Objective: To examine the effect that neoadjuvant axitinib for the treatment of localized renal cell carcinoma has on body compartment composition.Materials and Methods: The study was based on a single-institution, single-arm clinical trial that enrolled 24 patients with locally advanced non-metastatic biopsy-proven clear cell renal cell carcinoma. Patients received axitinib orally for up to 12 weeks. Computed tomography scans were completed before the start of treatment, after 7 weeks of treatment and at the completion of 12 weeks of treatment. Patients underwent nephrectomy after axitinib treatment. The primary outcome of the current study was change in body compartment composition. Secondary outcomes included development of new-onset sarcopenia and changes in body weight.Results: A total of 23 patients had a complete set of imaging for evaluation, of which 19 (82.6%) lost weight. Median weight loss was 4.5 kg (P <.001). Seven patients (30.4%) had sarcopenia before treatment, with an additional 5 (21.7%) developing sarcopenia during treatment. Median decrease in skeletal muscle was 2.9 cm2/m2 (P <.001), visceral adipose tissue was 4.9 cm2/m2 (P = .132), and subcutaneous adipose tissue was 1.0 cm2/m2 (P = .043). Ten of the 16 patients (62.5%) without baseline sarcopenia achieved a partial response, whereas only 1 of the 7 patients (14.3%) with baseline pretreatment sarcopenia achieved a partial response (P = .069).Conclusion: Neoadjuvant axitinib resulted in a decrease in skeletal muscle and subcutaneous adipose tissue, as well as weight loss. Patients with baseline sarcopenia tended to have a lower response rate to neoadjuvant axitinib. [ABSTRACT FROM AUTHOR]

The article presents a study that evaluates the occurrence of genetic counseling referral for ovarian cancer patients who were at risk of breast cancer type 1 or 2 (BRCA1 or BRCA2). The study collected data on the analysis of the ovarian cancer patients from January 1, 1999 to December 31, 2007. Results of the study reveal that 12% of patients were referred in 1999 and improved to 48% in 2007. The study concludes that the risk of BRCA1 or BRCA2 mutations and genetic counseling was inadequate.