National Comprehensive Cancer Network Guidelines Research Articles

SAT313 Therapeutic Dosing Of Steroids In Patients On Mitotane

Abstract Disclosure: C. Pham: None. S.M. Cannon: None. J.S. Lopresti: None. Introduction: Mitotane is a known inhibitor of steroidogenesis with some patients requiring supraphysiologic dosing for steroid replacement. Clinical Case: A 43-year-old female with a history of adrenal cell carcinoma (ACC) on multiagent chemotherapy and mitotane presents with a pruritic rash. Three weeks prior, she had received her first dose of pembrolizumab. Her other home medications included mitotane 500mg QID and hydrocortisone 180mg (40mg-40mg-30mg -20mg QID). Labs on admission were notable for an ALT of 458 (ref 10-35 U/L), AST of 272 (ref 10-35 U/L), and normal alkaline phosphatase and bilirubin with otherwise normal electrolytes. Due to the temporal relation of her transaminitis and rash to recent pembrolizumab infusion with an otherwise negative work-up, the patient was diagnosed with immune-mediated liver injury from checkpoint inhibitors (ILICI). Per National Comprehensive Cancer Network (NCCN) guidelines, high dose methylprednisolone was initiated (1mg/kg) equivalent to approximately 525 mg hydrocortisone total daily. Over five days, the patient’s transaminases continued to rise and methylprednisolone was increased to 3mg/kg/day to account for the known effects of mitotane on steroid metabolism. The patient’s rash subsequently resolved followed by slow improvement of her transaminitis with steroid taper. Mitotane level obtained one week after discontinuation of mitotane was noted to be 21mcg/mL demonstrating persistent therapeutic levels (14-20mcg/mL). Mitotane has a profound inhibitory effect on steroidogenesis through multiple mechanisms, inhibiting glucocorticoid production by the adrenal and increasing hepatic disposal of glucocorticoids leading to subtherapeutic doses1, Furthermore, mitotane can persist in the body for a prolonged period, with a half-life between 18-154 days. As such, patients who develop adrenal insufficiency on mitotane typically require higher doses for physiologic replacement up to three times standard physiologic dose1. In this case, only when the patient’s methylprednisolone dose was tripled did her ILICI begin to improve. Conclusion: This is one of the first cases to describe ILICI in a patient with ACC highlighting unique clinical considerations in management. Higher doses of corticosteroids may be required to overcome the effects of mitotane on steroid metabolism in patients with adverse effects from immune checkpoint inhibitor therapy. 1.)Puglisi, S., Calabrese, A., Basile, V., Pia, A., Reimondo, G., Perotti, P., & Terzolo, M. (2020). New perspectives for mitotane treatment of adrenocortical carcinoma. Best Practice & Research Clinical Endocrinology & Metabolism, 34(3), 101415. https://doi.org/10.1016/j.beem.2020.101415 Presentation: Saturday, June 17, 2023

Effects of Radiation Doses on Clinical Recurrence in Patients with Biochemically Recurrent Prostate Cancer after Prostatectomy.

Salvage radiotherapy (SRT) to the prostate bed is the only curative treatment for patients with biochemical recurrence (BCR) after radical prostatectomy (RP). Although several systematic reviews indicated that a dose escalation in the range of 60-70 Gy improved biochemical control, the effects of radiation doses on clinical relapse after SRT remain unclear. Our aim was to investigate the relationship between radiation doses and clinical relapse-free survival (cRFS) after SRT. We identified 295 eligible patients receiving SRT for biochemically recurrent prostate cancer after RP between 2005 and 2018 at 15 institutions. Sixteen patients (5%) received short-term (< 6 months) androgen deprivation therapy (ADT) following RP and/or concurrently with SRT. SRT was delivered to the prostate and seminal vesicle bed using photon beams at a median (range) dose of 66 Gy (61-85) in 1.8-3.0 Gy fractions. The primary outcome was cRFS. Clinical relapse was identified on radiological imaging and/or biopsy and included local recurrence, lymph node metastasis, and distant metastasis. In all analyses, doses were recalculated as an equivalent dose in 2-Gy fractions (EQD2) with α/β = 1.5 Gy. Clinical RFS between the EQD2 ≥ 66 Gy (n = 229) and EQD2 < 66 Gy (n = 66) groups were compared using the Log-rank test, followed by univariate and multivariate Cox regression analyses and a subgroup analysis. The median follow-up duration was 73 months. Among patients with BCR (n = 119), 79 of 96 (82%) in the EQD2 ≥ 66 Gy group and 21 of 23 (91%) in the EQD2 < 66 Gy group received second salvage ADT (p = 0.36). Among all patients (n = 295), clinical relapse was identified in 22 (7%) patients after SRT. Six-year biochemical relapse-free survival (bRFS), cRFS, cancer-specific survival (CSS), and overall survival (OS) rates were 58%, 93%, 98%, and 94%, respectively. Six-year cRFS rates were 94% (95% confidence interval [CI], 90-97) in the EQD2 ≥ 66 Gy group and 87% (95% CI, 75-93) in the EQD2 < 66 Gy group (p = 0.020). The multivariate analysis revealed that EQD2 < 66 Gy, Gleason score ≥ 8, seminal vesicle involvement, and PSA at BCR ≥ 0.5 ng/ml correlated with clinical relapse (p = 0.0016, 0.014, 0.011, and 0.027, respectively). The subgroup analysis showed the consistent benefit of EQD2 ≥ 66 Gy in patients across most subgroups including PSA at BCR after RP, extracapsular extension, and age at SRT. This large multi-institutional observational study demonstrated that a higher SRT dose (EQD2 ≥ 66 Gy) resulted in superior cRFS. The present result supports the dose recommendations in the 2023 National Comprehensive Cancer Network guidelines (64-72 Gy) even in terms of clinical relapse. Prospective trial is warranted to investigate an upper threshold for optimal SRT dose.

1938P Assessment of clinical benefit of cancer drugs recommended in National Comprehensive Cancer Network (NCCN) guidelines for advanced soft tissue sarcomas (STS) and bone sarcomas (BS)

1938P Assessment of clinical benefit of cancer drugs recommended in National Comprehensive Cancer Network (NCCN) guidelines for advanced soft tissue sarcomas (STS) and bone sarcomas (BS)

Insurance Plan Coverage Modeling of the Marginal Costs from One Week vs. Three Week Radiation Therapy in Standard-Of-Care Treatment of Post-Lumpectomy Early-Stage Breast Cancer Across Medicaid and Medicare Plans

For early-stage breast cancer (BC), the choice of radiation therapy (RT) duration (1- versus 3-weeks) is highly debated. Cost and financial toxicity are major concerns that BC patients face. Nonetheless, there remain limited discussions providing granular details of the role of insurance in the aggregate cost of 1 week versus 3 weeks of RT for patients. This project addresses this gap by disaggregating costs by insurance plan to increase transparency of out-of-pocket (OOP) cost estimates in RT. Surgical, medical, and radiation oncology treatment procedures were determined through the National Comprehensive Cancer Network guidelines; codes were identified using Current Procedural Terminology and Healthcare Common Procedure Coding System. OOP treatment costs, deductibles, and copay/coinsurance were calculated in accordance with insurance type, including Medicaid, Original Medicare, and Medigap Plan G. The medicare.gov, medicaid.oh.gov, and the physician fee schedule from cms.gov were used to determine pricing. Price estimates reflect actual costs per insurance plan rather than costs estimated from claims data. All procedures were considered to be performed in an Ohio hospital setting. One-week RT was defined as 5 fractions without boost, and 3-week RT was defined as 15 fractions without boost. Treatment charges for RT included initial radiation oncology office consultation and subsequent radiation oncology clinical treatment planning notes, complex 3D treatment plan, dosimetry calculations, complex treatment device design and construction, complex treatment planning simulation, simple verification treatment simulation, complex RT delivery, port verification films, on-treatment visits with radiation oncology, and continuing medical physics consultation. Original Medicare beneficiaries face an OOP cost of 20% for every Medicare Part B charge with no cost cap for all approved procedures after the deductible is met, resulting in a marginal OOP treatment charge of $649.24 for 1 week and $1006.20 for 3 weeks of RT. Assuming the deductible is met post-lumpectomy, Medigap Plan G beneficiaries are faced with no additional charges for both lengths of radiation treatment. Similarly, for Medicaid beneficiaries (assuming all treatments approved by Medicaid), all expenses are covered without limit, resulting in no OOP expense. Considerations of 1 week and 3 weeks of RT for post-lumpectomy early-stage BC are often dependent on cancer characteristic and patient preferences. This model (based on actual cost estimates per insurance plan rather than claims data) compares OOP costs across Medicaid and Medicare plans, which more holistically informs patients in their decision for choice of treatment.

Characterizing the Impact of Race and Redlining on Receipt of Guideline-Compliant Locoregional Therapy among Older Women with Breast Cancer

Breast cancer (BC) is one of few malignancies in which improved locoregional control has been shown to improve overall survival. Contemporary redlining, or mortgage lending bias on the basis of home location, is a form of structural racism which has been demonstrated to impact BC survival in older patients. Self-reported race has been thought to serve as a surrogate for interpersonal racism and has similarly been shown to have associations with survival, redlining, and access to care. We aim to examine the relationship between race, redlining, and the receipt of guideline compliant locoregional therapy (LRT) in older women with BC. Women aged 66-90 years with an initial Stage I-III BC diagnosis in 2010-2017 and known metropolitan statistical area (MSA) were identified in SEER-Medicare. Redlining was estimated using Home Mortgage Disclosure Act data (2010-2017). Guideline compliant LRT was assessed based on whether patients underwent surgery (lumpectomy or mastectomy), and if surgery was performed, whether they received adjuvant radiation treatment per the National Quality Forum and National Comprehensive Cancer Network guidelines in effect during the study period. A multiple logistic regression model was fitted to estimate ORs for the relationship between redlining and receipt of guideline compliant LRT, accounting for covariates (age, race/ethnicity, comorbidities, dual enrollment, tumor stage, hormone receptor status, census region, and year of diagnosis). Cluster bootstrap at the MSA-level was used to obtain P-values and confidence intervals. The cohort included 64,987 women: 31% aged 66-70, 82% Non-Hispanic (NH) White, 7.4% NH Black, 24% with 2+ comorbidities, 12% with dual Medicaid/Medicare enrollment, 60% stage I, 31% stage II, and 77% HR+/HER2-. Overall, 6.4% did not undergo surgery; 84% received guideline compliant LRT. Women in the highest redlining areas had 81% guideline compliant LRT compared to 84-85% in the least, low and moderate redlined areas (p<0.001). However, model results revealed that contemporary redlining was not a predictor of guideline compliant LRT. NH Black women were less likely than NH White women to receive guideline-compliant LRT (OR 0.77, 95% CI 0.71-0.84, p<0.001). No significant differences were noted between NH White and NH Asian or Hispanic women. In this population-based cohort of older women with breast cancer, NH Black race, even after adjusting for several important clinical and demographic factors, was associated with a lower likelihood of receiving guideline-compliant LRT. This finding demonstrates the profound impact of interpersonal racism on receipt of cancer-directed therapies. Though contemporary redlining did not significantly impact guideline-compliant LRT, further work is needed to identify systematic factors explaining known associations between contemporary redlining and BC survival.

Patterns of Care for Patients with Locally Advanced Rectal Cancer Treated with Total Neoadjuvant Therapy between 2016-2020: An NCDB Analysis

Treatment for locally advanced rectal cancer (LARC), defined as T3/4 or any T with N+ disease, typically requires multi-modality management consisting of radiation (RT), chemotherapy (CHT), and surgery. Despite emerging evidence that total neoadjuvant therapy (TNT) is the preferred treatment of LARC, it remains unknown what proportion of patients are receiving TNT in the United States. Our objective was to (1) determine the proportion of patients with LARC receiving TNT over time, (2) determine the most common method in which TNT is being delivered, and (3) determine what factors are associated with a lower likelihood of receiving TNT in the United States. Retrospective data was obtained from the National Cancer Database (NCDB) for patients diagnosed with rectal cancer between 2016-2020. Patients were excluded if they had M1 disease, T1-2 N0 disease, incomplete staging information, non-adenocarcinoma histology, received RT to a non-rectum site, or received a non-definitive RT dose. Patients were determined to have received TNT if they (1) received RT and multi-agent (MA)-CHT prior to surgery, (2) had an interval of >180 days from the onset of neoadjuvant therapy to surgery if they received long course (LC)-chemoradiation (CRT) (based on 35 days for LC-CRT + 112 days for 8 cycles of MA-CHT + 30 days to surgery), or (3) had an interval of >150 days from the onset of neoadjuvant therapy to surgery if they received short course (SC)-RT (based on 5 days for SC-RT + 112 days for 8 cycles of MA-CHT + 30 days to surgery). Data were analyzed using linear regression, Chi-square test, and binary logistic regression. Of the 26,375 patients included, the median age was 60 (range 21-90) years, with the majority of patients being <65 years old (65.6%), male (62.1%), and non-Hispanic white (77.0%). A total of 5,003 (19.0%) patients received TNT, and 21,372 (81.0%) patients received classical combined modality therapy (CMT). The proportion of patients receiving TNT increased significantly over time, from 6.1% in 2016, 9.0% in 2017, 15.3% in 2018, 25.8% in 2019, to 34.6% in 2020 (slope = 7.36, 95% CI 4.58-10.15, R2 = 0.96, p = 0.040). The most common TNT regimen was MA-CHT followed by LC-CRT (73.2% of cases from 2016-2020). The proportion of patients receiving SC-RT as part of TNT significantly increased from 2.8% in 2016, 1.7% in 2017, 4.6% in 2018, 7.3% in 2019, to 13.7% in 2020 (slope = 2.74, 95% CI 0.37-5.11, R2 = 0.82, p = 0.035). On multivariate analysis, factors associated with a lower likelihood of TNT use included age >65 (OR 0.66, 95% CI 0.61-0.71, p<0.001), female gender (OR 0.92, 95% CI 0.86-0.98, p = 0.014), Black race (OR 0.87, 95% CI 0.77-0.98, p = 0.024), and T3 N0 disease (OR 0.60, 95% CI 0.52-0.70, p<0.001). TNT utilization rates have significantly increased in recent years, from 6.1% in 2016 to 34.6% in 2020. The observed trend appears to be in line with the recent National Comprehensive Cancer Network (NCCN) guidelines recommending TNT as the preferred approach.

Prognostic factor analysis and clinical significance of HER‑2‑positive breast cancers with negative lymph nodes and a tumor diameter ≤1cm.

The 2021 National Comprehensive Cancer Network guidelines recommend that adjuvant chemotherapy combined with trastuzumab be considered for human epidermal growth factor receptor 2 (HER-2)-positive breast cancer patients with small tumors (tumor diameter ≤1 cm) and negative lymph nodes. Additionally, the prognostic factors and clinical significance of HER-2-positive breast cancer with negative lymph nodes and a tumor diameter ≤1 cm remain unclear. In the present study, the clinical data and prognostic factors of 87 patients with HER-2-positive breast cancer with negative lymph nodes and a tumor diameter ≤1 cm admitted to Guangdong Women and Children Hospital from January 2013 to December 2019 were retrospectively analyzed. The median follow-up time was 70 months, the disease-free survival (DFS) of all patients was 94.3% and the overall survival (OS) was 100%. Univariate analysis of prognosis demonstrated that patients aged ≤40 years had significantly lower DFS than those aged >40 (80.8 vs. 100.0%, P<0.001). DFS was significantly improved in patients who were hormone-receptor-positive and patients who received endocrine therapy compared with patients who were estrogen receptor negative and patients who did not receive endocrine therapy (100.0 vs. 89.6%, P=0.039; 100.0 vs. 90.0%, P=0.049). Prognostic univariate analysis demonstrated that patient age, hormone receptor status and use of endocrine therapy were significantly related to the DFS (P<0.05), while none of these were independent factors related to the DFS in the prognostic multivariate analysis (P=0.240, P=0.976 and P=0.925). The proportion of patients with a tumor diameter 0.5-1 cm receiving adjuvant anti-HER-2 treatment was significantly greater compared with patients with tumors with a diameter ≤0.5 cm (46.4 vs. 18.6%, P<0.05). There was no significance difference in the DFS of patients treated with adjuvant chemotherapy with or without anti-HER-2 therapy with tumor diameters ≤0.5 cm (P>0.05), but there was a significant difference in the DFS of patients with a tumor diameter 0.5-1 cm (P<0.05). These results suggested that adjuvant chemotherapy, with or without anti-HER-2 therapy, may affect the prognosis of HER-2-positive breast cancer patients with negative lymph nodes and a tumor diameter of 0.5-1 cm. Therefore, it could be recommended that such patients receive adjuvant chemotherapy and anti-HER-2 therapy in the future.

Out-of-Pocket Cost Modeling of Adjuvant Radiation Therapy Duration in Standard-of-Care Early Stage Breast Cancer Treatment Across Medicaid and Medicare Plans

For early-stage breast cancer (BC), the choice of radiotherapy duration (1- versus 3-weeks) is highly debated. Cost and financial toxicity are major concerns that BC patients face. Nonetheless, there remain limited discussions providing granular details of the role of insurance in the aggregate cost of 1 week versus 3 weeks of radiotherapy for patients. This project aims to disaggregate costs by plan to increase transparency of out-of-pocket (OOP) cost estimates in radiotherapy. Treatment procedures were determined through the National Comprehensive Cancer Network guidelines. OOP treatment costs, deductibles, and copays/coinsurance were calculated by utilizing Medicaid, Original Medicare, Medigap Plan G and Medicare Part D Rx plans. The medicare.gov, medicaid.oh.gov, aarpmedicareplans.com, and the physician fee schedule from cms.gov were used to determine costs by treatment. Price estimates reflect actual costs per insurance plan rather than costs estimated from claims data. All procedures were considered to be performed in an Ohio hospital setting. One-week radiotherapy was defined as 5 fractions without boost, and 3-week radiotherapy was defined as 15 fractions without boost. Medicare beneficiaries with Original Medicare coverage face an OOP treatment charge of $649.24 for one-week radiotherapy and $1006.20 for three-weeks of radiotherapy. Assuming the deductible is met post-lumpectomy, Medigap Plan G beneficiaries are faced with no additional charges for both lengths of radiotherapy. Similarly, for Medicaid beneficiaries (assuming treatment is approved by Medicaid), all expenses are covered without limit, resulting in no OOP expense. Considerations of one- and three-weeks of radiotherapy for post-lumpectomy early-stage BC are often dependent on cancer characteristics and patient preferences. This model (based on actual cost estimates per insurance plan rather than claims data) compares OOP costs across Medicaid and Medicare plans, which more holistically informs providers and patients in radiotherapy duration decision-making.

Assessment of adherence to National Comprehensive Cancer Network guideline recommended anticoagulant therapy in the management of patients with cancer-associated venous thromboembolic disease

Assessment of adherence to National Comprehensive Cancer Network guideline recommended anticoagulant therapy in the management of patients with cancer-associated venous thromboembolic disease

Assessment of adherence to National Comprehensive Cancer Network guideline recommended anticoagulant therapy in the management of patients with cancer-associated venous thromboembolic disease

Assessment of adherence to National Comprehensive Cancer Network guideline recommended anticoagulant therapy in the management of patients with cancer-associated venous thromboembolic disease

The minimum number of examined lymph nodes was 24 for optimal survival of pathological T2-4 gastric cancer: a multi-center, hospital-based study covering 20 years of data

IntroductionThe current National Comprehensive Cancer Network (NCCN) guidelines recommend that at least 16 lymph nodes should be examined for gastric cancer patients to reduce staging migration. However, there is still debate regarding the optimal management of examined lymph nodes (ELNs) for gastric cancer patients. In this study, we aimed to develop and test the minimum number of ELNs that should be retrieved during gastrectomy for optimal survival in patients with gastric cancer.MethodsWe used the restricted cubic spline (RCS) to identify the optimal threshold of ELNs that should be retrieved during gastrectomy based on the China National Cancer Center Gastric Cancer (NCCGC) database. Northwest cohort, which sourced from the highest gastric cancer incidence areas in China, was used to verify the optimal cutoff value. Survival analysis was performed via Kaplan-Meier estimates and Cox proportional hazards models.ResultsIn this study, 12,670 gastrectomy patients were included in the NCCGC cohort and 4941 patients in the Northwest cohort. During 1999–2019, the average number of ELNs increased from 17.88 to 34.45 nodes in the NCCGC cohort, while the number of positive lymph nodes remained stable (5–6 nodes). The RCS model showed a U-curved association between ELNs and the risk of all-cause mortality, and the optimal threshold of ELNs was 24 [Hazard ratio (HR) = 1.00]. The ELN ≥ 24 group had a better overall survival (OS) than the ELN < 24 group clearly (P = 0.003), however, with respect to the threshold of 16 ELNs, there was no significantly difference between the two groups (P = 0.101). In the multivariate analysis, ELN ≥ 24 group was associated with improved survival outcomes in total gastrectomy patients [HR = 0.787, 95% confidence interval (CI): 0.711–0.870, P < 0.001], as well as the subgroup analysis of T2 patients (HR = 0.621, 95%CI: 0.399–0.966, P = 0.035), T3 patients (HR = 0.787, 95%CI: 0.659–0.940, P = 0.008) and T4 patients (HR = 0.775, 95%CI: 0.675–0.888, P < 0.001).ConclusionIn conclusion, the minimum number of ELNs for optimal survival of gastric cancer with pathological T2-4 was 24.

Delays Starting Postoperative Radiotherapy Among Head and Neck Cancer Patients: A Systematic Review and Meta-analysis.

Initiating postoperative radiotherapy (PORT) within 6 weeks (42 days) of surgery is the first and only Commission on Cancer (CoC) approved quality metric for head and neck squamous cell carcinoma (HNSCC). No study has systematically reviewed nor synthesized the literature to establish national benchmarks for delays in starting PORT. Following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we performed a systematic review of PubMed, Scopus, and CINAHL. Studies that described time-to-PORT or PORT delays in patients with HNSCC treated in the United States after 2003 were included. Meta-analysis of proportions and continuous measures was performed on nonoverlapping datasets to examine the pooled frequency of PORT delays and time-to-PORT. Thirty-six studies were included in the systematic review and 14 in the meta-analysis. Most studies utilized single-institution (n = 17; 47.2%) or cancer registry (n = 16; 44.4%) data. Twenty-five studies (69.4%) defined PORT delay as >6 weeks after surgery (the definition utilized by the CoC and National Comprehensive Cancer Network Guidelines), whereas 4 (11.1%) defined PORT delay as a time interval other than >6 weeks, and 7 (19.4%) characterized time-to-PORT without defining delay. Meta-analysis revealed that 48.6% (95% confidence interval [CI], 41.4-55.9) of patients started PORT > 6 weeks after surgery. Median and mean time-to-PORT were 45.8 (95% CI, 42.4-51.4 days) and 47.4 days (95% CI, 43.4-51.4 days), respectively. Delays in initiating guideline-adherent PORT occur in approximately half of patients with HNSCC. These meta-analytic data can be used to set national benchmarks and assess progress in reducing delays.

Pathologic Nodal Staging Before SBRT for Early-stage NSCLC Does Not Impact Overall Survival: A Propensity Score-matched NCDB Analysis.

Stereotactic body radiation therapy (SBRT) for early-stage non-small cell carcinoma of the lung (NSCLC) is increasingly utilized. We sought to assess overall survival (OS) for early-stage NSCLC patients receiving SBRT depending on staging method. Early-stage NSCLC patients treated with definitive SBRT were identified in the National Cancer Database (NCDB), and OS was determined based on method of staging. Patient, disease, and treatment characteristics were also analyzed. A total of 12,106 patients were included; 865 (7%) received invasive staging (nodal sampling, NS) and 11,241 (93%) had no nodal sampling (NNS). From this larger dataset, a propensity score matching (1:1 without replacement) was performed, which yielded 839 patients for each group (NNS and NS). With a median follow-up time of 3.12 years, median survival for all patients included in the matched dataset was 2.75 years (95% CI: 2.55-2.93y), with 2- and 5-year OS estimated at 63.9% and 25.7%, respectively. In a multivariable analysis on matched data, there was no difference in mortality risk between the NNS and NS groups (hazard ratio=1.08, 95% CI: 0.94-1.24, P =0.25). Negative prognostic factors identified in the multivariable analysis of the matched data included: age more than 65, male sex, Charlson-Deyo Score ≥1, and tumor size ≥3cm. SBRT use in early-stage NSCLC steadily increased over the study period. Most patients proceeded to SBRT without nodal staging, conflicting with National Comprehensive Cancer Network (NCCN) guidelines which recommend pathologic mediastinal lymph node evaluation for all early-stage NSCLC cases, except stage IA. Our findings suggest similar OS in patients with early-stage NSCLC treated with SBRT irrespective of nodal staging. Furthermore, we highlight patient-related, disease-related, and treatment-related prognostic factors to consider when planning therapy for these patients.

Familial genetic cancer risk assessment in a male patient with pancreatic and breast cancer with a silent BRCA2 mutation

Male breast cancer (MBC) is relatively rare, accounting for &lt;1% of cancers in men. Hereditary MBC is mainly attributed to BRCA1/2 germline mutations. Accordingly, National Comprehensive Cancer Network guidelines advise genetic counseling and testing for all cases of MBCs and their unaffected family members. In this report, we present an uncommon case of a male patient in his late 50s primarily diagnosed with pancreatic cancer who later developed asynchronous bilateral hormone-positive breast cancer. Genetic testing revealed a “pathogenic/likely pathogenic” BRCA2 variant (c.8754G &gt;A, pE2918E) in the proband. Cascade testing of 34 family members identified 5 of the family members as carriers of this BRCA2 variant. Among them, two members were breast cancer affected and three were unaffected healthy carriers. Our study demonstrates the clinical relevance of this silent BRCA2 mutation and emphasizes the need for further experimental studies to elucidate its functional role in breast cancer pathology.

Immediate reconstruction of nasal alar defects after malignant skin tumor excision without mohs surgery

Objectives: The National Comprehensive Cancer Network guidelines state that any nasal region with squamous or basal cell skin cancer is at high risk. Although Mohs surgery is the gold-standard procedure for many types of skin cancer, it is not applicable worldwide. A mean of 1.7 Mohs surgery stage is performed in cases of tumors. Nasal obstruction is a problem with Mohs surgery. In this study, we aimed to investigate nasal alar region nonmelanoma malignant skin tumor excision using immediate reconstruction without Mohs surgery. Methods: Ten patients underwent reconstruction surgery between 2018 and 2022. The inclusion criterion were ulcerated lesions in the nasal alar region measuring less than 1 cm in diameter, the lesions which were suspected either as basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) on dermatoscopic examination, the patients who had intact nasal mucosa during anterior rhinoscopy. Results: The mean follow-up duration was 26 months. No patient required re-operation because of an excisional biopsy result that involved border proximity. We observed no serious complications or long-term recurrences. Conclusion: We recommend our algorithm for patients for whom Mohs surgery is not applicable.

Exploring Breast Cancer Systemic Drug Therapy Patterns in Real-World Data.

To explore medications and their administration patterns in real-world patients with breast cancer. A retrospective study was performed using TriNetX, a federated network of deidentified, Health Insurance Portability and Accountability Act-compliant data from 21 health care organizations across North America. Patients diagnosed with breast cancer between January 1, 2013, and May 31, 2022, were included. We investigated a rule-based and unsupervised learning algorithm to extract medications and their administration patterns. To group similar administration patterns, we used three features in k-means clustering: total number of administrations, median number of days between administrations, and standard deviation of the days between administrations. We explored the first three lines of therapy for patients classified into six groups on the basis of their stage at diagnosis (early as stages I-III v late as stage IV) and the sensitivity of the tumor's receptors to targeted therapies: hormone receptor-positive/human epidermal growth factor 2-negative (HR+/ERBB2-), ERBB2-positive (ERBB2+/HR±), or triple-negative (TN; HR-/ERBB2-). To add credence to the derived regimens, we compared them to the National Comprehensive Cancer Network (NCCN): Breast Cancer (version 2.2023) recommendations. In early-stage HR+/ERBB2- and TN groups, the most common regimens were (1) cyclophosphamide and docetaxel, administered once every 3 weeks for three to six cycles and (2) cyclophosphamide and doxorubicin, administered once every 2 weeks for four cycles, followed by paclitaxel administered once every week for 12 cycles. In the early-stage ERBB2+/HR± group, most patients were administered carboplatin and docetaxel with or without pertuzumab and with trastuzumab (for six or more cycles). Medications most commonly administered in our data set (7,798 patients) agreed with recommendations from the NCCN in terms of medications (regimens), number of administrations (cycles), and days between administrations (cycle length). Although there is a general agreement with the NCCN Guidelines, real-world medication data exhibit variability in the medications and their administration patterns.

Genetic counseling and testing for females at elevated risk for breast cancer: Protocol for the randomized controlled trial of the Know Your Risk intervention

BackgroundGenetic counseling and testing have an important role in the care of patients at elevated risk for breast cancer. However, conventional pre- and post-test genetic counseling is labor and time intensive, less accessible for patients living outside major urban centers, and impractical on a large scale. A patient-driven approach to genetic counseling and testing may increase access, improve patients' experiences, affect efficiency of clinical practice, and help meet workforce demand. The objective of this 2-arm randomized controlled trial is to determine the efficacy of Know Your Risk (KYR), a genetic counseling patient preference intervention. MethodsFemales (n = 1000) at elevated risk (>20% lifetime) for breast cancer will be randomized to the KYR intervention or conventional genetic counseling. The study will provide comprehensive assessment of breast cancer risk by multigene panel testing and validated polygenic risk score. Primary outcome is adherence to National Comprehensive Cancer Network guidelines for a clinical encounter every 6–12 months and an annual mammogram (breast MRI if recommended) determined by medical record review. Secondary outcomes include adherence to other recommended cancer screening tests determined by medical record review and changes in breast cancer knowledge, perception of risk, post-test/counseling distress, and satisfaction with counseling by completion of three surveys during the study. Study aims will be evaluated for non-inferiority of the KYR intervention compared to conventional genetic counseling. ConclusionIf efficacious, the KYR intervention has the potential to improve patients' experience and may change how genetic counseling is delivered, inform best practices, and reduce workforce burden.Trial Registration: ClinicalTrials.govNCT05325151

Hyperthermic intrapleural chemotherapy: an update.

The safety and efficacy of hyperthermic intrathoracic chemotherapy (HITHOC) as an adjunct to cytoreductive surgery (CRS) in pleural malignancies has been well demonstrated. This is most often described in cases of mesothelioma, thymoma, or other secondary pleural metastases. The utilization of a direct cytotoxic agent with increased penetration secondary to a hyperthermic environment is especially beneficial in pleural malignancy as a microscopic resection remains immensely challenging. Despite favorable outcomes with a limited associated risk profile, there persists a variety in utilization and technique of HITHOC described in current literature. National Comprehensive Cancer Network (NCCN) guidelines state that though intraoperative adjuvant therapies such as HITHOC have been studied, they remain of unclear benefit and definitive recommendations do not currently exist. This ambiguity limits the standardization of HITHOC, thus hindering its further application in a patient population with exceedingly poor outcomes within current guideline-based therapy. As the prevalence of pleural malignancies necessitating CRS with adjuvant HITHOC remains quite low, we believe a task force initiative to further investigate the role of HITHOC in surgical management of pleural malignancies would enable wider utility of this promising technique. Additionally, we propose that the creation of a pleural cancer index could aid in standardization of HITHOC in those with pleural malignancy.

Management of Benign Phyllodes Tumors: A Dutch Population-Based Retrospective Cohort Between 1989 and 2022.

Phyllodes tumors (PTs) are rare tumors of the breast. The current National Comprehensive Cancer Network (NCCN) guidelines recommend excision of benign PTs, accepting close or positive margins. Controversy about the optimal treatment for benign PTs remains, especially regarding the preferred margin width after surgical excision and the need for follow-up evaluation. A nationwide retrospective study analyzed the Dutch population from 1989 to 2022. All patients with a diagnosis of benign PT were identified through a search in the Dutch nationwide pathology databank (Palga). Information on age, year of diagnosis, size of the primary tumor, surgical treatment, surgical margin status, and local recurrence was collected. The study enrolled 1908 patients with benign PT. The median age at diagnosis was 43 years (interquartile range [IQR], 34-52 years), and the median tumor size was 30 mm (IQR, 19-40 mm). Most of the patients (95%) were treated with breast-conserving surgery (BCS). The overall local recurrence rate was 6.2%, and the median time to local recurrence was 31 months (IQR, 15-61 months). Local recurrence was associated with bilaterality of the tumor (odds ratio [OR], 4.91; 95% confidence interval [CI], 2.95-28.30) and positive margin status (OR, 2.51; 95% CI 1.36-4.63). The local recurrence rate was 8.9% for the patients with positive excision margins and 4.0% for the patients with negative excision margins. Notably, for 27 patients (22.6%) who experienced a local recurrence, histologic upgrading of the recurrent tumor was reported, 7 (5.9%) of whom had recurrence as malignant lesions. This nationwide series of 1908 patients showed a low local recurrence rate of 6.2% for benign PT, with higher recurrence rates following positive margins.

Use of Artificial Intelligence Chatbots for Cancer Treatment Information

This survey study examines the performance of a large language model chatbot in providing cancer treatment recommendations that are concordant with National Comprehensive Cancer Network guidelines.