Management of Patients With Advanced Gastrointestinal Stromal Tumor: Emphasis on Fourth-Line Treatment With Ripretinib.

Gastrointestinal stromal tumors (GISTs) are considered rare, yet they represent the most common sarcomas of the gastrointestinal tract. The development of tyrosine kinase inhibitors (TKI) for the treatment of GISTs changed the way we treat patients and has greatly impacted outcomes. However, most patients who initially benefit from TKIs eventually develop disease progression and require subsequent therapies. Ripretinib is a switch-control TKI approved for the treatment of adult patients with advanced GIST who received prior treatment with three or more TKIs, including imatinib. Our objective was to review existing treatment options for patients with advanced GIST, focusing on management optimization for heavily pretreated patients receiving ripretinib. With the integration of ripretinib as a fourth-line therapy, the GIST treatment landscape continues to evolve. As the treatment paradigm becomes increasingly complex, successful management of adverse events and individualized supportive care remain crucial to maintaining effective treatment and patient quality of life. Additionally, we present a detailed case study of a heavily pretreated patient with advanced GIST who received ripretinib as fourth-line therapy. The information provided here should help inform advanced practitioners on the effective management of patients with GIST who have progressed on multiple therapies. Advanced practitioners are well positioned to provide the necessary supportive care to achieve optimal outcomes and drug compliance.

Retrospective analysis of adjuvant treatment for localized, operable uterine leiomyosarcoma.

OBJECTIVE: Currently, there is no standard adjuvant treatment protocol for localized uterine leiomyosarcoma (uLMS) as clinical trials to address this question have been retrospective, underpowered, or undermined by slow accrual rates. The aim of this study is to determine the benefit of adjuvant chemotherapy for uLMS. METHODS: We reviewed the medical records of localized uLMS patients who had underwent adjuvant therapy after upfront surgery between 2000 and 2020. The cases were blinded for review. We evaluated the influence of various clinical characteristics and different types of adjuvant therapies on specific outcomes. RESULTS: Sixty-eight patients (median age: 50 years) were included for analysis. Forty of 68 (58.8%) patients received adjuvant chemotherapy +/- radiation therapy and 25 patients (38.6%) did not receive any adjuvant therapy. At a median follow-up time of 43.3 months, 45 patients (66.1%) had relapsed disease. The median disease-free survival (mDFS) for all patients was 23.1 months. Patients who received any adjuvant treatment (chemotherapy and/or radiation) trended toward a longer mDFS compared with those who did not receive any adjuvant therapy (29.7 vs. 14.1 months, p = 0.26). Patients who received adjuvant chemotherapy alone had a longer, but nonstatistically significant mDFS compared with those who did not receive any adjuvant treatment (22.2 vs. 14.1 months, p = 0.18). Additionally, univariate analysis found that tumor size large than 10 cm, and a mitotic rate >10/10hpf were independent prognostic factors for worse DFS. CONCLUSIONS: Though DFS was more favorable among those who received adjuvant therapy, it was not statistically significant, and thus based on this data adjuvant therapy for resected uLMS is still in question.

A Randomized Phase II Study of Nivolumab Monotherapy or Nivolumab Combined with Ipilimumab in Patients with Advanced Gastrointestinal Stromal Tumors.

PURPOSE: Most gastrointestinal stromal tumors (GIST) are driven by KIT/PDGFRa mutations. Tyrosine kinase inhibitor benefit is progressively less after imatinib failure. This phase II trial analyzed the efficacy of nivolumab (N) or nivolumab + ipilimumab (N + I) in patients with refractory GIST. PATIENTS AND METHODS: Patients with advanced/metastatic GIST refractory to at least imatinib were randomized 1:1 in a noncomparative, parallel group, unblinded phase II trial of N (240 mg every 2 weeks) or N + I (240 mg every 2 weeks + 1 mg/kg every 6 weeks). The primary endpoint was the objective response rate of N alone or N+I by RECIST 1.1 in the intent-to-treat population. RESULTS: A total of 36 patients with a median of 3 (1-6) prior lines of therapies were enrolled. Ten of 19 (52.6%) patients had stable disease (SD) for a clinical benefit rate (CBR) of 52.6% in the N arm and the median progression-free survival (PFS) was 11.7 weeks [95% confidence interval (CI), 7.0-17.4]. In the N+I arm, 1 of 16 (6.7%) patients had a complete response (CR) and 4/16 (25.0%) had SD for a CBR of 31.3% and a median PFS of 8.3 weeks (95% CI, 5.6-22.2). The 4- and 6-month PFS were 42.1% and 26.3%, respectively for N, and 31.3% and 18.8%, respectively for N+I. The most common adverse events (AE) attributed to N and N+I were fatigue: 13.9% and 22.2%, respectively. There were nine total attributable grade 3-4 AEs. CONCLUSIONS: The primary endpoint of response rate > 15% was not observed for N or N + I. In a heavily pretreated GIST population, responses and long-term disease control with both N and N+I were observed. No new safety signals have been observed.

Colorectal cancer metastasis presenting as a testicular mass: case report and review of the literature.

Metastatic lesions to the testicle are uncommon. The authors report a testicular mass as the initial manifestation of distant metastasis from colorectal cancer. This case describes a 51-year-old white man who presented with an enlarged right testicle 9 months after undergoing a right hemicolectomy for a stage IIIC colon adenocarcinoma. The diagnostic and management strategy is discussed. In addition, the literature is reviewed to characterize this uncommon entity further. Although rare, testicular metastasis must be considered in patients with previously resected colorectal carcinoma.

Comparative morbidity of axillary lymph node dissection and the sentinel lymph node technique: implications for patients with breast cancer.

OBJECTIVE: To assess our long-term complications from complete axillary lymph node dissection (AXLND) in patients with breast cancer. SUMMARY BACKGROUND DATA: Complete AXLND as part of the surgical therapy for breast cancer has come under increased scrutiny due the use of the sentinel lymph node (SLN) biopsy technique to assess the status of the axillary nodes. As the enthusiasm for the SLN technique has increased, our impression has been that the perceived complication rate from AXLND has increased dramatically while the negative aspects of the SLN technique have been underemphasized. METHODS: Female patients seen in routine follow-up over a 1-year period were eligible for our retrospective study of the long-term complications from AXLND if they were a minimum of 1 year out from all primary therapy; ie, surgery, radiation, and/or chemotherapy. All patients had previously undergone either a modified radical mastectomy (MRM) or a segmental mastectomy with axillary dissection and postoperative radiation (SegAx/XRT). All patients had a Level I-III dissection. Objective measurements, including upper and lower arm circumferences and body mass index (BMI), were obtained, and a subjective evaluation from the patients was conducted. RESULTS: Ninety-four patients were eligible for our study; 44 had undergone MRM, and 50 had undergone SegAx/XRT. The average number of nodes removed was 25.6 (standard deviation, 8). Thirty-three percent of the patients had positive nodal disease, 95% of the patients had an upper arm circumference within 2 cm of the unaffected side, and 93.3% had a lower arm circumference within 2 cm of the unaffected side. Subjectively, 90.4% of the patients had either no or minimal arm swelling, and 96.8% of the patients had "good" or "excellent" overall arm function. The most common long-term symptom was numbness involving the upper, inner aspect of the affected arm (25.5%). CONCLUSIONS: Our data indicate that a complete AXLND can be performed with minimal long-term morbidity. The lower the morbidity of AXLND, the less acceptable are the unique complications of the SLN technique.