Purpose
Preoperative and postoperative RT for the treatment of high-grade soft-tissue sarcoma result in similar local control and overall survival rates, but morbidities differ. Postoperative RT is ...associated with a higher rate of long-term fibrosis, edema, and joint stiffness. Preoperative RT is associated with higher rates of wound complications. It is important to identify predictors for major wound complications (MWC) and to develop strategies to minimize this outcome. We reviewed our experience to determine predictors for MWC following preoperative radiotherapy (RT) and surgery for soft-tissue sarcoma.
Methods
Between January 2006 and May 2011, 103 patients with soft-tissue sarcoma of the extremities and trunk were treated with preoperative RT followed by surgery. MWCs were defined as those requiring operative or prolonged nonoperative management. Fisher’s exact test was used to compare rates. Logistic regression was used for multivariable analysis of factors potentially associated with MWCs.
Results
Median tumor size was 8.4 cm (range 2–25). All patients had wide or radical resections. Wound closures were primary in 70 %, a vascularized flap in 27 %, and split-thickness skin graft (STSG) in 3 %. There were 36 MWCs (35 %). Significant predictors for MWCs on univariate analysis included diabetes, tumors >10 cm, tumors <3 mm from skin surface, and vascularized flap/STSG closure. The same four variables were significant predictors on multivariable analysis.
Conclusions
MWCs following preoperative RT and surgery were common. Tumor proximity to skin surface <3 mm is a previously unreported independent predictor, and further strategies to minimize wound complications are needed.
Cutaneous radiation therapy (RT)-associated breast angiosarcoma (AS) is a rare consequence of breast RT associated with poor outcomes. Previous small case series have documented high recurrence rates ...and poor survival. We reviewed our experience and focused on the impact of conservative versus radical resections.
Data for patients with RT-associated breast AS evaluated at our institution from 1993 to 2015 who underwent surgery were reviewed.
Seventy-six women were diagnosed with RT-associated breast AS at a median 85 months from surgery for invasive breast carcinoma or ductal carcinoma in situ. Thirty-eight underwent mastectomy/wide excision with partial skin resection ("conservative") and 38 underwent resection of all or nearly all previously irradiated skin plus mastectomy ("radical"). The radical group (vs the conservative group) more often had multifocal disease (80% vs 56%, P = 0.04), chemotherapy for AS (58% vs 22%, P < 0.01), margin-negative resection (100% vs 73%, P < 0.01), reconstructive surgery (100% vs 13%, P < 0.01), and re-operation (16% vs 3%, P = 0.04). Five-year crude cumulative incidences of local recurrence and distant metastasis for radical versus conservative groups were 23% versus 76% (P < 0.01) and 18% versus 47% (P = 0.02), respectively. Five-year disease-specific survival (DSS) for radical versus conservative groups was 86% versus 46% (P < 0.01), respectively. On multivariable analysis, age, radicality of surgery, and margin were predictive of DSS.
For patients with RT-associated breast AS, radical resection was associated with reduced recurrence rates and improved DSS. Although margin was predictive of DSS, multifocality calls into question the reliability of negative margin assessment.
Shortly before I was elected President of ASCO, I attended the 65th birthday party of a current patient. She had been diagnosed 10 years earlier with metastatic breast cancer and hadn't been sure she ...wanted to move forward with further treatment. With encouragement, she elected to participate in a clinical trial of an investigational drug that is now widely used to treat breast cancer. Happily, here we were, celebrating with her now-married daughters, their husbands, and three beautiful grandchildren, ages 2, 4, and 8. Such is the importance of clinical trials and promising new therapies.Clinical research is about saving and improving the lives of individuals with cancer. It's a continuing story that builds on the efforts of untold numbers of researchers, clinicians, caregivers, and patients. ASCO's
report tells part of this story, sharing the most transformative research of the past year. The report also includes our latest thinking on the most urgent research priorities in oncology.ASCO's 2020 Advance of the Year-Refinement of Surgical Treatment of Cancer-highlights how progress drives more progress. Surgery has played a fundamental role in cancer treatment. It was the only treatment available for many cancers until the advent of radiation and chemotherapy. The explosion in systemic therapies since then has resulted in significant changes to when and how surgery is performed to treat cancer. In this report, we explore how treatment successes have led to less invasive approaches for advanced melanoma, reduced the need for surgery in renal cell carcinoma, and increased the number of patients with pancreatic cancer who can undergo surgery.Many research advances are made possible by federal funding. With the number of new US cancer cases set to rise by roughly a third over the next decade, continued investment in research at the national level is crucial to continuing critical progress in the prevention, screening, diagnosis, and treatment of cancer.While clinical research has translated to longer survival and better quality of life for many patients with cancer, we can't rest on our laurels. With ASCO's Research Priorities to Accelerate Progress Against Cancer, introduced last year and updated this year, we've identified the critical gaps in cancer prevention and care that we believe to be most pressing. These priorities are intended to guide the direction of research and speed progress.Of course, the effectiveness or number of new treatments is meaningless if patients don't have access to them. High-quality cancer care, including clinical trials, is out of reach for too many patients. Creating an infrastructure to support patients is a critical part of the equation, as is creating connections between clinical practices and research programs. We have much work to do before everyone with cancer has equal access to the best treatments and the opportunity to participate in research. I know that ASCO and the cancer community are up for this challenge.Sincerely,Howard A. "Skip" Burris III, MD, FACP, FASCOASCO President, 2019-2020.
Clinical trials provide evidence essential for progress in health care, and as the complexity of medical care has increased, the demand for such data has dramatically expanded. Conducting clinical ...trials has also become more complicated, evolving to meet increasing challenges in delivering clinical care and meeting regulatory requirements. Despite this, the general approach to data collection remains the same, requiring that researchers submit clinical data in response to study treatment protocols, using precisely defined data structures made available in study-specific case report forms. Currently, research data management is not integrated within the patient’s clinical care record, creating added burden for clinical staff and opportunities for error. During the past decade, the electronic health record has become standard across the US healthcare system and is increasingly used to collect and analyze data reporting quality metrics for clinical care delivery. Recently, electronic health record data have also been used to address clinical research questions; however, this approach has significant drawbacks due to the unstructured and incomplete nature of current electronic health record data. This report describes steps necessary to use the electronic health record as a tool for conducting high-quality clinical research.
The US National Cancer Act of 1971 designated the director of the National Cancer Institute as responsible for coordinating federal agencies and nonfederal organizations to make progress against ...cancer. As part of her role, the immediate past director of the National Cancer Institute (MMB) led the development of a National Cancer Plan that was formally released on April 3, 2023. The plan includes 8 aspirational goals "to achieve a society where every person with cancer lives a full and active life and to prevent most cancers so that few people need to face this diagnosis." Research findings provide a foundation for each goal, and research gaps are included in the strategies for meeting each goal. The President's Cancer Panel, also created by the National Cancer Act, conducted an initial assessment of progress toward the plan goals by hearing from 12 organizations at a virtual public meeting on September 7, 2023. The purpose of this commentary is to orient the scientific community to the plan and call attention to related knowledge gaps that could benefit from research.
Wide adoption of electronic health records (EHRs) has raised the expectation that data obtained during routine clinical care, termed "real-world" data, will be accumulated across health care systems ...and analyzed on a large scale to produce improvements in patient outcomes and the use of health care resources. To facilitate a learning health system, EHRs must contain clinically meaningful structured data elements that can be readily exchanged, and the data must be of adequate quality to draw valid inferences. At the present time, the majority of EHR content is unstructured and locked into proprietary systems that pose significant challenges to conducting accurate analyses of many clinical outcomes. This article details the current state of data obtained at the point of care and describes the changes necessary to use the EHR to build a learning health system.
To refine treatment recommendations for patients with metastatic gastrointestinal stromal tumors (GISTs) treated with tyrosine kinase inhibitors (TKIs) and surgery.
Early reports suggested that ...patients with metastatic GIST responding to TKIs treated with surgery may have favorable outcomes. However, identification of prognostic factors was limited by small cohorts.
Progression-free survival (PFS) and overall survival (OS) from time of surgery and from start of initial TKI was determined. Multivariate analysis was conducted on all patients undergoing GIST metastasectomy between 2001 and 2014 at 2 institutions.
We performed 400 operations on 323 patients with metastatic GIST on TKIs. Radiographic response at time of surgery was classified as responsive disease (RD, n = 64, 16%), stable disease (SD, n = 100, 25%), unifocal progressive disease (UPD, n = 132, 33%), and multifocal progressive disease (MPD, n = 104, 26%). For patients on imatinib before surgery, radiographic response was predictive of PFS from time of surgery (RD 36 months, SD 30 months, UPD 11 months, MPD 6 months; P < 0.001) and from imatinib initiation (RD 71 months, SD 51 months, UPD 47 months, MPD 33 months; P < 0.001). Radiographic response was predictive of OS from time of surgery (RD not reached, SD 110 months, UPD 59 months, MPD 24 months; P < 0.001), and from imatinib initiation (RD not reached, SD 144 months, UPD 105 months, MPD 66 months; P = 0.005). Radiographic response was not predictive of PFS/OS for patients on sunitinib. Metastatic mitotic index ≥5/50 HPF, MPD, and R2 resection were prognostic of worse PFS/OS; primary mutation was not.
Surgery in metastatic GIST patients in the absence of MPD on imatinib is associated with outcomes at least comparable with second-line sunitinib and may be considered in select patients.
Abstract Background The incidence of histopathologic organ invasion (HOI) in retroperitoneal sarcoma (RPS) is not well described. We reviewed our experience to investigate the rate and prognostic ...implications of HOI. Study Design Patients with primary RPS who underwent surgery at our institution were reviewed. HOI was defined as microscopic organ invasion confirmed by re-review of pathology slides by an expert sarcoma pathologist. Impact of HOI on the crude cumulative incidence (CCI) of locoregional recurrence (LRR), distant recurrence (DR) and overall survival (OS) rates was analyzed. Results Between 2002 and 2011, 118 patients underwent resection for primary RPS; 99 had at least one organ resected and among those, HOI was present in 58% (57/99). Among the 77 patients with the 3 most common histologies, rates of HOI were 61% for dedifferentiated liposarcoma, 56% for leiomyosarcoma, and 40% for well-differentiated liposarcoma. In this subset, HOI was associated with no difference in 2-year CCI of LRR (48% v. 47%, P =0.55) or DR (46% v. 22%, P =0.2). With a median follow-up of 33.6 months, HOI was an independent predictor of worse 5-year OS (34% v. 62%, P =0.04; hazard ratio 2.3, 95% confidence interval 1.2-4.4, P =0.02). Conclusions The likelihood of organ invasion may be predicted by histologic subtype of primary RPS. To the best of our knowledge, this is first study to demonstrate that HOI is associated with worse OS. These data may help guide the minimal extent of surgical resection required for RPS.
Alterations in the RAS and RAF pathway relate to epigenetic and epigenomic aberrations, and are important in colorectal carcinogenesis. KRAS mutation in metastatic colorectal cancer predicts ...resistance to anti-epidermal growth factor receptor (EGFR)-targeted therapy (cetuximab or panitumumab). It remains uncertain, however, whether KRAS mutation predicts prognosis or clinical outcome of colon cancer patients independent of anti-EGFR therapy.
We conducted a study of 508 cases identified among 1,264 patients with stage III colon cancer who enrolled in a randomized adjuvant chemotherapy trial (5-fluorouracil, leucovorin with or without irinotecan) in 1999-2001 (CALGB 89803). KRAS mutations were detected in 178 tumors (35%) by pyrosequencing. Kaplan-Meier and Cox proportional hazard models assessed the prognostic significance of KRAS mutation and adjusted for potential confounders including age, sex, tumor location, tumor/node stage, performance status, adjuvant chemotherapy arm, and microsatellite instability status.
Compared with patients with KRAS-wild-type tumors, patients with KRAS-mutated tumors did not experience any difference in disease-free, recurrence-free, or overall survival. The 5-year disease-free, recurrence-free, and overall survival rates (KRAS-mutated versus KRAS-wild-type patients) were 62% versus 63% (log-rank P = 0.89), 64% versus 66% (P = 0.84), and 75% versus 73% (P = 0.56), respectively. The effect of KRAS mutation on patient survival did not significantly differ according to clinical features, chemotherapy arm, or microsatellite instability status, and the effect of adjuvant chemotherapy assignment on outcome did not differ according to KRAS status.
In this large trial of chemotherapy in stage III colon cancer patients, KRAS mutational status was not associated with any significant influence on disease-free or overall survival.
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