Use of SPY angiography in tissue assessment for wound healing outcomes after breast reconstruction.

OBJECTIVE: The objective of this study was to evaluate whether a systematic image assessment protocol using SPY Elite images (LifeCell Corp., US) of viable tissue at the periphery of the surgical field was associated with positive wound healing outcomes following mastectomy and breast reconstruction. METHOD: Patients undergoing mastectomy and subsequent breast reconstruction surgery at a single tertiary medical centre were included. SPY images were prospectively analysed using a systematic image assessment protocol, and an absolute value of mean fluorescence was calculated by measuring peripheral, in-situ tissue from each image. Patient medical records were retrospectively reviewed for demographics, surgical characteristics and postoperative outcomes. These variables were statistically tested for associations with mean fluorescence. RESULTS: A total of 63 patients were included in the final analysis. We found that objectively determined mean fluorescence values were not statistically significantly associated with postoperative complications. CONCLUSION: In this study, objectively measured mean fluorescence values representing breast tissue remaining after dissection showed little utility in the assessment of postoperative wound healing outcomes as they did not identify patients who would later have complications of wound healing. DECLARATION OF INTEREST: The authors have no conflicts of interest to declare.

Neoadjuvant cobimetinib and atezolizumab with or without vemurafenib for high-risk operable Stage III melanoma: the Phase II NeoACTIVATE trial.

Both targeted therapies and immunotherapies provide benefit in resected Stage III melanoma. We hypothesized that the combination of targeted and immunotherapy given prior to therapeutic lymph node dissection (TLND) would be tolerable and drive robust pathologic responses. In NeoACTIVATE (NCT03554083), a Phase II trial, patients with clinically evident resectable Stage III melanoma received either 12 weeks of neoadjuvant vemurafenib, cobimetinib, and atezolizumab (BRAF-mutated, Cohort A, n = 15), or cobimetinib and atezolizumab (BRAF-wild-type, Cohort B, n = 15) followed by TLND and 24 weeks of adjuvant atezolizumab. Here, we report outcomes from the neoadjuvant portion of the trial. Based on intent to treat analysis, pathologic response (≤50% viable tumor) and major pathologic response (complete or near-complete, ≤10% viable tumor) were observed in 86.7% and 66.7% of BRAF-mutated and 53.3% and 33.3% of BRAF-wild-type patients, respectively (primary outcome); these exceeded pre-specified benchmarks of 50% and 30% for major pathologic response. Grade 3 and higher toxicities, primarily dermatologic, occurred in 63% during neoadjuvant treatment (secondary outcome). No surgical delays nor progression to regional unresectability occurred (secondary outcome). Peripheral blood CD8 + TCM cell expansion associated with favorable pathologic responses (exploratory outcome).

Omission of axillary lymph node dissection for breast cancer patients with three or more positive sentinel lymph nodes.

PURPOSE: The ACOSOG Z0011 (Z11) trial assessed the benefit of axillary dissection (ALND) for breast cancer patients with sentinel lymph node (SLN) metastases; however, Z11 excluded patients with ≥ 3 positive SLNs. We analyzed trends in ALND omission in patients with ≥ 3 positive SLNs. METHODS: Women with ≥ 3 positive SLNs who underwent breast-conserving surgery (BCS) or mastectomy between 2018 and 2020 in the National Cancer Database were included using SLN codes initiated in 2018. Patients with stage IV disease, recurrent breast cancer, and who underwent neoadjuvant chemotherapy were excluded. A multivariable logistic regression model was utilized to determine the proportion who received ALND and factors associated with ALND omission. A subgroup analysis was performed among patients who met the remainder of the Z11 inclusion criteria (BCS, T1/T2 breast cancer). RESULTS: We identified 3654 patients with ≥ 3 positive SLNs. ALND was omitted in 37% of patients, and omission significantly increased from 2018 to 2020 (29% vs. 41%, p < 0.0001). Older age, lower grade tumors, no radiation, non-academic facility, BCS, more SLNs examined and fewer positive SLNs were significantly associated with ALND omission. 942 patients with ≥ 3 positive SLNs met the remainder of the Z11 inclusion criteria. ALND was omitted in 49% of these patients, and omission increased from 2018 to 2020 (44% vs. 49%, p = 0.22). CONCLUSION: Approximately one-third of patients with ≥ 3 positive SLNs do not undergo ALND; omission of ALND increased from 2018 to 2020. Studies assessing oncologic outcomes of patients with ≥ 3 positive SLNs who do and do not receive ALND are required.

A nationwide analysis of disparities in guideline-concordant care in American Indians and Alaska Natives with stage I non-small cell lung cancer.

Background: Several studies have shown racial disparities in lung cancer care in the United States in the Black and Hispanic populations but not many have included American Indian/Alaska Native (AI/AN) patients. We retrospectively evaluated the factors associated with receipt of guideline-concordant care in AI/AN and non-Hispanic White (NHW) patients with stage I non-small cell lung cancer (NSCLC) and describe the relationship between guideline-concordant care and survival outcomes in these populations. Methods: Using the National Cancer Database, we identified NHW and AI/AN patients diagnosed with stage I NSCLC between 2004 and 2017. We evaluated the utilization of anatomic resection among both NHW and AI/AN and described the variables associated with anatomic resection. We also evaluated 5-year overall survival (OS) by treatment and race. We used the chi-square test, multivariable analysis, and the Kaplan-Meier method for statistical analysis. Results: We identified 196,349 patients. Of these, 195,736 (99.69%) were NHW and 613 (0.31%) were AI/AN. Relative to NHW, AI/AN were more frequently diagnosed at a younger age (40% vs. 28% diagnosed at 18-64 years of age; P<0.001) and more commonly resided in rural areas (14% vs. 5%; P<0.001). In our multivariable analysis adjusting for all patient factors [age at diagnosis, sex, race, residence location, Charlson Comorbidity Index (CCI), tumor stage, lymph node status, and treatment facility], AI/AN patients were less likely to undergo anatomic resection than NHW patients [odds ratio (OR), 0.74; 95% confidence interval (CI): 0.62-0.89]. In our unadjusted survival analysis, AI/AN patients had lower 5-year OS than NHW (58% vs. 56%; P=0.04). When adjusted for surgery this difference was no longer significant. Conclusions: AI/AN patients with stage I NSCLC undergo anatomic resection less frequently than do NHW, with lower 5-year OS than NHW. However, this survival difference is mitigated when AI/AN undergo anatomic resection.

Readability Analysis of Online Breast Cancer Surgery Patient Education Materials from National Cancer Institute-Designated Cancer Centers Compared with Top Internet Search Results.

BACKGROUND: The National Institutes of Health (NIH) recommends patient education materials reflect the average reading grade level of the US population. Due to the importance of shared decision-making in breast cancer surgery, this study evaluates the reading level of patient education materials from National Cancer Institute-designated cancer centers (NCI-DCC) compared with top Internet search results. METHODS: Online materials from NCI-DCC and top Internet search results on breast cancer, staging, surgical options, and pre- and postoperative expectations were analyzed using three validated readability algorithms: Simplified Measure of Gobbledygook Readability Formula, Coleman-Liau index, and Flesch-Kincaid grade level. Mean readability was compared across source groups and information subcategories using an unpaired t-test with statistical significance set at p < 0.05. Mean readability was compared using a one-way analysis of variance. RESULTS: Mean readability scores from NCI-DCC and Internet groups ranged from a 9th-12th grade level, significantly above the NIH recommended reading level of 6th-7th grade. There was no significant difference between reading levels from the two sources. The discrepancy between actual and recommended reading level was most pronounced for "surgical options" at a 10th-12th grade level from both sources. CONCLUSIONS: Patient education materials on breast cancer from both NCI-DCC and top Internet search results were written several reading grade levels higher than the NIH recommendation. Materials should be revised to enhance patient comprehension of breast cancer surgical treatment and guide patients in this important decision-making process to ultimately improve health outcomes.

Disparities in post-mastectomy reconstruction use among American Indian and Alaska Native women.

BACKGROUND: American Indian/Alaska Native (AI/AN) breast cancer patients undergo post-mastectomy reconstruction (PMR) infrequently relative to Non-Hispanic White (NHW) patients. Factors associated with low PMR rates among AI/AN are poorly understood. We sought to describe factors associated with this disparity in surgical care. METHODS: A retrospective cohort study of the National Cancer Database (2004 - 2017) identified AI/AN and NHW women, ages 18 - 64, who underwent mastectomy for stage 0 - III breast cancer. Patient characteristics, annual PMR rates, and factors associated with PMR were described with univariable analysis, the Cochran-Armitage test, and multivariable logistical regression. RESULTS: 414,036 NHW and 1,980 AI/AN met inclusion criteria. Relative to NHW, AI/AN had more comorbidities (20% vs 12% Charlson Comorbidity Index ≥ 1, p < 0.001), had non-private insurance (49% vs 20%, p < 0.001), and underwent unilateral mastectomy more frequently (69% vs 61%, p < 0.001). PMR rates increased over the study period, from 13% to 47% for AI/AN and from 29% to 62% for NHW (p <0.001). AI/AN race was independently associated with decreased likelihood of PMR (OR 0.62, 95% CI 0.56-0.69). Among AI/AN, decreased likelihood of PMR was significantly associated with older age at diagnosis, more remote year of diagnosis, advanced disease (tumor size > 5 cm, positive lymph nodes), unilateral mastectomy, non-private insurance, and lower educational attainment in patient's area of residence. CONCLUSION: PMR rates among AI/AN with stage 0 - III breast cancer have increased, yet remain significantly lower than among NHW. Further research should elicit AI/AN perspectives on PMR, and guide early breast cancer detection and treatment.

Availability of cancer care services and the organization of care delivery at critical access hospitals.

INTRODUCTION: Critical access hospitals (CAHs) provide an opportunity to meet the needs of individuals with cancer in rural areas. Two common innovative care delivery methods include the use of traveling oncologists and teleoncology. It is important to understand the availability and organization of cancer care services in CAHs due to the growing population with cancer and expected declines in oncology workforce in rural areas. METHODS: Stratified random sampling was used to generate a sample of 50 CAHs from each of the four U.S. Census Bureau-designated regions resulting in a total sample of 200 facilities. Analyses were conducted from 135 CAH respondents to understand the availability of cancer care services and organization of cancer care across CAHs. RESULTS: Almost all CAHs (95%) provided at least one cancer screening or diagnostic service. Forty-six percent of CAHs reported providing at least one component of cancer treatment (chemotherapy, radiation, or surgery) at their facility. CAHs that offered cancer treatment reported a wide range of health care staff involvement, including 34% of respondents reporting involvement of a local oncologist, 38% reporting involvement of a visiting oncologist, and 28% reporting involvement of a non-local oncologist using telemedicine. CONCLUSION: Growing disparities within rural areas emphasize the importance of ensuring access to timely screening and guideline-recommended treatment for cancer in rural communities. These data demonstrated that CAHs are addressing the growing need through a variety of approaches including the use of innovative models that utilize non-local providers and telemedicine to expand access to crucial services for rural residents with cancer.

Theranostics application of tumor-initiating cell probe TiY in non-small cell lung cancer.

Background: Tumor-initiating cells (TIC) often elude conventional cancer treatment, which results in metastasis and cancer relapse. Recently, studies have begun to focus on the TIC population in tumors to provide better therapeutic options. Previously, we have reported the successful development of a TIC-specific probe TiY with the binding target as vimentin. While a low concentration of TiY showed a TIC visualization, at a high concentration, TiY induced selective toxicity onto TIC in vitro. In this study, we aim to assess TiY's applicability in theranostics purposes, from in vivo visualization to therapeutic effect toward TIC, in cancer mouse models. Methods: We performed cell experiments with the TIC line model derived from resected primary non-small cell lung cancer (NSCLC) patient tumor. The animal model studies were conducted in mice of NSCLC patient-derived xenograft (PDX). TiY was intravenously delivered into the mice models at different concentrations to assess its in vivo TIC-selective staining and therapeutic effect. Results: We demonstrated the TIC-selective identification and therapeutic effect of TiY in animal models. TiY treatment induced a significant ablation of the TIC population in the tumor, and further molecular study elucidated that the mechanism of TiY is through vimentin dynamics in TIC. Conclusion: The results underscore the applicability of TiY for cancer treatment by selectively targeting soluble vimentin in TIC.

Chemotherapy refusal and subsequent survival in healthy older women with high genomic risk estrogen receptor-positive breast cancer.

BACKGROUND: Patients with estrogen receptor (ER)-positive, HER2-negative breast cancer (BC), and high-risk 21-gene recurrence score (RS) results benefit from chemotherapy. We evaluated chemotherapy refusal and survival in healthy older women with high-RS, ER-positive BC. METHODS: Retrospective review of the National Cancer Database (2010-2017) identified women ≥ 65 years of age, with ER-positive, HER2-negative, high-RS (≥ 26) BC. Patients with Charlson Comorbidity Index ≥ 1, stage III/IV disease, or incomplete data were excluded. Women were compared by chemotherapy receipt or refusal using the Cochrane-Armitage test, multivariable logistical regression modeling, the Kaplan-Meier method, and Cox's proportional hazards modeling. RESULTS: 6827 women met study criteria: 5449 (80%) received chemotherapy and 1378 (20%) refused. Compared to women who received chemotherapy, women who refused were older (71 vs 69 years), were diagnosed more recently (2014-2017, 67% vs 61%), and received radiation less frequently (67% vs 71%) (p ≤ 0.05). Refusal was associated with decreased 5-year OS for women 65-74 (92% vs 95%) and 75-79 (85% vs 92%) (p ≤ 0.05), but not for women ≥ 80 years old (84% vs 91%; p = 0.07). On multivariable analysis, hazard of death increased with refusal overall (HR 1.12, 95% CI 1.04-1.2); but, when stratified by age, was not increased for women ≥ 80 years (HR 1.10, 95% CI 0.80-1.51). CONCLUSIONS: Among healthy women with high-RS, ER-positive BC, chemotherapy refusal was associated with decreased OS for women ages 65-79, but did not impact the OS of women ≥ 80 years old. Genomic testing may have limited utility in this population, warranting prudent shared decision-making and further study.

International Center-Level Variation in Utilization of Completion Lymph Node Dissection and Adjuvant Systemic Therapy for Sentinel Lymph Node-Positive Melanoma at Major Referral Centers.

OBJECTIVE: The aim of this study was to determine overall trends and center-level variation in utilization of completion lymph node dissection (CLND) and adjuvant systemic therapy for sentinel lymph node (SLN)-positive melanoma. SUMMARY BACKGROUND DATA: Based on recent clinical trials, management options for SLN-positive melanoma now include effective adjuvant systemic therapy and nodal observation instead of CLND. It is unknown how these findings have shaped practice or how these contemporaneous developments have influenced their respective utilization. METHODS: We performed an international cohort study at 21 melanoma referral centers in Australia, Europe, and the United States that treated adults with SLN-positive melanoma and negative distant staging from July 2017 to June 2019. We used generalized linear and multinomial logistic regression models with random intercepts for each center to assess center-level variation in CLND and adjuvant systemic treatment, adjusting for patient and disease-specific characteristics. RESULTS: Among 1109 patients, performance of CLND decreased from 28% to 8% and adjuvant systemic therapy use increased from 29 to 60%. For both CLND and adjuvant systemic treatment, the most influential factors were nodal tumor size, stage, and location of treating center. There was notable variation among treating centers in management of stage IIIA patients and use of CLND with adjuvant systemic therapy versus nodal observation alone for similar risk patients. CONCLUSIONS: There has been an overall decline in CLND and simultaneous adoption of adjuvant systemic therapy for patients with SLN-positive melanoma though wide variation in practice remains. Accounting for differences in patient mix, location of care contributed significantly to the observed variation.

Adult Hematology/Oncology Patient Perspectives on Telemedicine Highlight Areas of Focus for Future Hybrid Care Models.

Introduction: Telemedicine use expanded rapidly during the COVID-19 pandemic, but publications analyzing patient perspectives on telemedicine are few. We aimed to study whether patient perspectives offer insights into how best to utilize telemedicine in the future for hematology and cancer care. Methods: A modified Telemedicine Satisfaction and Usefulness Questionnaire (TSUQ) was sent to adult hematology/oncology outpatients at the University of Minnesota Masonic Cancer Clinic who had ≥1 prior phone and/or video visit between March 15, 2020, and March 31, 2021. Two focus groups were subsequently conducted with volunteers who completed the survey. We evaluated dichotomized TSUQ items using logistic regression, and focus group data were analyzed qualitatively using constant comparison analysis. Results: Of 7,848 invitations, 588 surveys were completed. Focus groups included 16 survey respondents. Most respondents found telemedicine satisfactory, easy to use, and convenient, with the majority preferring a hybrid approach going forward. Oncology patients, females, and higher income earners endorsed decreased telemedicine satisfaction. Concerns were voiced about fewer in-person interactions, communication gaps, and provider style variability. Discussion: Adult hematology/oncology patients had varied perspectives on telemedicine utilization success based on gender, income, and disease burden, suggesting that a one-size-fits-all approach, as was implemented nearly universally during the COVID-19 pandemic, is not an ideal approach for the long term. Given that telemedicine use is likely to remain in some form in most centers, our findings suggest that a nuanced and tailored approach for some patient subgroups and using feedback from patients will make implementation more effective.

Outcomes with adjuvant anti-PD-1 therapy in patients with sentinel lymph node-positive melanoma without completion lymph node dissection.

Until recently, most patients with sentinel lymph node-positive (SLN+) melanoma underwent a completion lymph node dissection (CLND), as mandated in published trials of adjuvant systemic therapies. Following multicenter selective lymphadenectomy trial-II, most patients with SLN+ melanoma no longer undergo a CLND prior to adjuvant systemic therapy. A retrospective analysis of clinical outcomes in SLN+ melanoma patients treated with adjuvant systemic therapy after July 2017 was performed in 21 international cancer centers. Of 462 patients who received systemic adjuvant therapy, 326 patients received adjuvant anti-PD-1 without prior immediate (IM) CLND, while 60 underwent IM CLND. With median follow-up of 21 months, 24-month relapse-free survival (RFS) was 67% (95% CI 62% to 73%) in the 326 patients. When the patient subgroups who would have been eligible for the two adjuvant anti-PD-1 clinical trials mandating IM CLND were analyzed separately, 24-month RFS rates were 64%, very similar to the RFS rates from those studies. Of these no-CLND patients, those with SLN tumor deposit >1 mm, stage IIIC/D and ulcerated primary had worse RFS. Of the patients who relapsed on adjuvant anti-PD-1, those without IM CLND had a higher rate of relapse in the regional nodal basin than those with IM CLND (46% vs 11%). Therefore, 55% of patients who relapsed without prior CLND underwent surgery including therapeutic lymph node dissection (TLND), with 30% relapsing a second time; there was no difference in subsequent relapse between patients who received observation vs secondary adjuvant therapy. Despite the increased frequency of nodal relapses, adjuvant anti-PD-1 therapy may be as effective in SLN+ pts who forego IM CLND and salvage surgery with TLND at relapse may be a viable option for these patients.

The Addition of Chemoradiation to Adjuvant Chemotherapy is Associated With Improved Survival Following Upfront Surgical Resection for Pancreatic Cancer With Nodal Metastases.

BACKGROUND: It is unclear whether the addition of chemoradiation (CRT) to adjuvant chemotherapy (CT) following upfront resection of pancreatic ductal adenocarcinoma (PDAC) provides any benefit. While some studies have suggested a benefit to combined modality therapy (CMT) (adjuvant CT plus CRT), it is not clear if this benefit was related to increased CT usage in patients who received CMT. We sought to clarify the use of CMT in patients who underwent upfront resection of PDAC. METHODS: Patients with non-metastatic PDAC were retrospectively identified from the linked SEER-Medicare database. Those who underwent upfront resection were identified and divided into two cohorts - patients who received adjuvant CT and patients who received adjuvant CMT. Cohorts were compared. Univariate analysis described patient characteristics. Kaplan-Meier and multivariable Cox proportional hazards modeling were used to estimate overall survival (OS). RESULTS: 3555 patients were identified; 856 (24%) received CT and 573 (16%) received CMT. The median number of CT doses was 11 for both groups. Patients who received CMT were younger, diagnosed in the earlier time frame, and had fewer comorbidities. The median OS was 21 months and 18 months for those treated with CMT and CT (P < .0001), respectively, but when stratified by nodal status, the association with improved OS in the CMT cohort was only observed in node-positive patients. On multivariable analysis, receipt of CMT and removal of >15 lymph nodes decreased the risk of death (P < .05). DISCUSSION: Receipt of CMT following upfront resection for PDAC was associated with improved survival, which was confined to node-positive patients. The role of adjuvant CMT in PDAC with nodal metastases warrants further study.

The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases - A multicenter cohort study.

PURPOSE: Guidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics. METHODS: A multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions. RESULTS: A total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4-12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively. CONCLUSION: Systemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies.

How to Treat Breast Cancer After Childhood Cancer: Management of Oncologic and Cardiovascular Concerns.

•Childhood cancer survivors are at higher risk for the development of breast cancer necessitating early breast cancer screening, often with both breast MRI and mammography.•Risk-stratify breast cancer treatment, taking into account prior radiation fields, surgical procedures, use of anthracyclines, and current comorbidities is essential.•Aggressive management of CV risk factors in collaboration with cardiologists, oncologists, primary care providers, and allied health care providers is needed to provide the best cancer treatment while optimizing CV health.

Perception of Telehealth During the COVID-19 Pandemic Among Survivors of Gynecologic Cancer.

Our objective was to assess gynecologic cancer survivor preferences for telehealth cancer care. Gynecologic cancer survivors participating in a prospective cohort study were invited to complete a cross-sectional survey regarding their experience with and preferences for telehealth. Of 188 participants, 48.9% had undergone a telehealth visit since March 2020, and 53.7% reported a preference for exclusively in-person visits for their cancer care and surveillance. Furthermore, 80.5% of participants were satisfied with the telehealth care they received and 54.8% would recommend telehealth services to patients with similar conditions. Most participants thought a physical examination was critical to detecting recurrence, and concern that their provider may miss something during telehealth visits was greater among those who preferred in-person visits. With many gynecologic cancer survivors preferring in-person care, building a future care model that includes telehealth elements will require adaptations, careful evaluation of patient concerns, as well as patient education on telehealth.