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Purpose of Review : Antibody–drug conjugates (ADCs) are a class of therapeutics that combine target-specific monoclonal antibodies with cytotoxic chemotherapy. Here, we describe the components of ADCs and review their promising activity, safety, and applicability in non-small cell lung cancer (NSCLC). Recent Findings: Technological advancements have reinvigorated ADCs as a viable treatment strategy in advanced solid tumors. Several target-specific ADCs have shown promise in treatment-refractory NSCLC, including agents targeting HER2, HER3, TROP2, CEACAM5, and MET, among others, with multiple confirmatory phase 3 trials ongoing. Critically, ADCs have demonstrated efficacy signals in both driver mutation-positive and mutation-negative advanced NSCLC, reinforcing their potential as an efficacious treatment strategy that transcends diverse tumor biology in advanced NSCLC. Summary: ADCs are a promising class of anti-cancer therapeutics that have significant potential in advanced NSCLC. Beyond confirmatory phase 3 trials, several questions remain including optimal agent sequencing, combinatorial methods, and unique toxicity management. [ABSTRACT FROM AUTHOR]

Purpose: Breast cancer diagnosis at a very young age has been independently correlated with worse outcomes. Appropriately intensifying treatment in these patients is warranted, even as we acknowledge the risks of potentially mutagenic adjuvant therapies. We examined local control, distant control, overall survival, and secondary malignancy rates by age cohort and by initial surgical strategy.Methods and Materials: Female patients less than or equal to 35 years of age diagnosed with invasive breast cancer from January 1, 1990, to December 31, 2010, were identified. Control groups of those aged 36 to 50 years (n = 6246) and 51 to 70 years (n = 7294) were delineated from an institutional registry. Clinicopathologic and follow-up information was collected. Chi-squared test was used to compare frequencies of categorical variables. Survival endpoints were evaluated using Kaplan-Meier methodology.Results: A total of 529 patients ≤35 years of age met criteria for analysis. The median age of diagnosis was 32 years (range 20-35). Median follow-up was 10.3 years. On multivariable analysis, factors associated with overall survival (OS) were tumor size (hazard ratio [HR] 1.14, P = .02), presence of lymphovascular invasion (HR 2.2, P <.001), estrogen receptor positivity (HR 0.64, P = .015), receipt of adjuvant chemotherapy (HR 0.52, P = .035), and black race (HR 2.87, P <.001). The ultra-young were more likely to experience local failure compared with the aged 36 to 50 group (HR 2.2, 95% CI 1.8-2.6, P < .001) and aged 51 to 70 group (HR 3.1, 95% CI 2.45 - 3.9, P <.001). The cumulative incidence of secondary malignancies at 5 and 10 years was 2.2% and 4.4%, respectively. Receipt of radiation was not significantly associated with secondary malignancies or contralateral breast cancer.Conclusion: Survival and recurrence outcomes in breast cancer patients ≤35 years are worse compared with those aged 36 to 50 or 51 to 70 years. Based on our data, breast conservation therapy is appropriate for these patients, and the concern for second malignancies should not impinge on the known indications for postoperative radiation therapy. [ABSTRACT FROM AUTHOR]

Purpose: Most studies examining accelerated partial breast irradiation (APBI) have used twice-daily fractionation. Cosmesis with this approach has produced mixed results, and the optimal fractionation scheme remains unknown. We sought to evaluate the safety and efficacy of APBI with a total dose of 40 Gy in 10 daily fractions.Methods and Materials: Between 2010 and 2014, we prospectively enrolled 106 patients to receive APBI after lumpectomy for invasive or in situ node-negative breast cancer. Radiation was administered via 3-dimensional conformal techniques.Results: The median age was 62 years (range, 39-85), and all patients underwent APBI per protocol. With a median follow-up of 58 months, we evaluated patient-reported local toxicity and recurrence outcomes. Of 106 patients, 16 (15%) experienced grade ≥2 skin toxicity. The most common significant toxicities were acute cutaneous changes at 4 to 9 weeks after radiation therapy, including grade 2 erythema in 2 patients (1.8%) and skin color changes in 4 patients (3.8%). Only 2 instances of grade 3 toxicity were reported, including 1 patient with acute moist desquamation after radiation therapy and another with fibrosis at 2 years. Planning target volume and breast V20 were significantly predictive of skin/subcutaneous toxicity, with evidence that limiting breast V20 to <45% may improve tolerability. Overall, 3 breast cancer recurrences arose: 1 local recurrence in the original quadrant (3 years after APBI), 1 in a different ipsilateral quadrant (5 years after APBI), and 1 with distant disease 2 years after APBI.Conclusions: In an appropriately selected group of patients with early stage breast cancer, APBI to a dose of 40 Gy in 10 daily fractions was well tolerated, with most patients (99%) reporting excellent/good cosmesis. Planning target volume and breast V20 should be carefully constrained to limit local morbidity. Longer follow-up will be needed to establish efficacy and subsequent local recurrence rates. [ABSTRACT FROM AUTHOR]

Purpose: A 2-arm, double-blinded randomized trial was conducted to evaluate the efficacy of 0.1% mometasone furoate (MF) versus Eucerin Original (E) cream in preventing the development of moderate to severe acute radiation dermatitis (ARD) in breast cancer patients receiving postmastectomy radiation (PMRT).Methods: Breast cancer patients undergoing chest wall with or without nodal radiation therapy (RT) (50 Gy) were eligible. Randomization (1:1) was to MF or E, applied twice daily from day 1 of PMRT to 14 days after PMRT. Patients were stratified by RT technique, body mass index, and reconstruction status. Daily bolus of 3 to 10 mm was applied in all patients. The primary endpoint was the development of provider-assessed grade ≥2 (Common Terminology Criteria for Adverse Events version 4.03) ARD with moist desquamation or any grade ≥3 dermatitis. Secondary endpoints were time to occurrence of maximum-grade dermatitis and patient-reported skin symptoms using a skin-related quality of life questionnaire, Skindex-16. Assessments were performed at baseline, weekly during PMRT, and 2 weeks after PMRT.Results: 124 patients were enrolled between May 2013 and February 2016. Of those, 35% had pathologic stage III disease, 6% had cT4d disease, and 68% underwent reconstruction. Sixty percent received 3-dimensional conformal RT with photons only to the chest wall, 18% received electrons and photons, and 23% received inverse-planned intensity modulated RT. Groups were well balanced for age, skin type, and stage. The rate of moist desquamation was 54.8% in the entire cohort, with a significantly reduced incidence in the MF arm than in the E arm (43.8% vs 66.7%; P = .012). The MF arm had a lower incidence of maximum skin toxicities (P = .036) and longer time to development of grade 3 dermatitis (46 days vs 35.5 days, respectively; P ≤ .001). There was no difference in patient-reported skin outcomes between arms.Conclusions: Breast cancer patients receiving MF during PMRT experienced significantly reduced rates of moist desquamation in comparison with a control cream. [ABSTRACT FROM AUTHOR]

Purpose: Capsular contracture (CC) is a serious complication in patients receiving implant-based reconstruction for breast cancer. Currently, no objective methods are available for assessing CC. The goal of the present study was to identify image-based surrogates of CC using magnetic resonance imaging (MRI).Methods and Materials: We analyzed a retrospective data set of 50 patients who had undergone both a diagnostic MRI scan and a plastic surgeon's evaluation of the CC score (Baker's score) within a 6-month period after mastectomy and reconstructive surgery. The MRI scans were assessed for morphologic shape features of the implant and histogram features of the pectoralis muscle. The shape features, such as roundness, eccentricity, solidity, extent, and ratio length for the implant, were compared with the Baker score. For the pectoralis muscle, the muscle width and median, skewness, and kurtosis of the intensity were compared with the Baker score. Univariate analysis (UVA) using a Wilcoxon rank-sum test and multivariate analysis with the least absolute shrinkage and selection operator logistic regression was performed to determine significant differences in these features between the patient groups categorized according to their Baker's scores.Results: UVA showed statistically significant differences between grade 1 and grade ≥2 for morphologic shape features and histogram features, except for volume and skewness. Only eccentricity, ratio length, and volume were borderline significant in differentiating grade ≤2 and grade ≥3. Features with P<.1 on UVA were used in the multivariate least absolute shrinkage and selection operator logistic regression analysis. Multivariate analysis showed a good level of predictive power for grade 1 versus grade ≥2 CC (area under the receiver operating characteristic curve 0.78, sensitivity 0.78, and specificity 0.82) and for grade ≤2 versus grade ≥3 CC (area under the receiver operating characteristic curve 0.75, sensitivity 0.75, and specificity 0.79).Conclusions: The morphologic shape features described on MR images were associated with the severity of CC. MRI has the potential to further improve the diagnostic ability of the Baker score in breast cancer patients who undergo implant reconstruction. [ABSTRACT FROM AUTHOR]