Interplay of Oncoplastic Reconstruction and Adjuvant Radiation Therapy in Breast Cancer.

Purpose: Oncoplastic breast surgery (OBS) combines breast cancer tumor removal with the cosmetic benefits of plastic surgery at the time of breast-conserving surgery. Potential advantages of OBS include wider surgical margins around the tumor bed, while the natural shape and appearance of the breast are maintained more than standard lumpectomy procedures. However, limited information is available regarding the potential effect on adjuvant radiation treatment planning. Materials and Methods: Women with localized breast cancer undergoing lumpectomy with immediate OBS and adjuvant radiation therapy between 2014 and 2019 were reviewed. OBS was performed using volume displacement techniques and patients received whole-breast irradiation with 3-dimensional conformal radiation therapy. Results: Volume of additional ipsilateral breast tissue removed during OBS ranged from 21 to 2086 cm3 (median, 304 cm3), 29% of patients had >500 cm3 of tissue removed. Surgical margins were positive in 12.5% and were not affected by volume of breast tissue removed (445 vs 439 cm3). Patients with surgical clips more often received a lumpectomy bed boost (75.9% vs 50.0%), boost volumes were on average 157 cm3 with clips versus 205 cm3 without clips. Mean V105 was comparable in patients with >500 cm3 tissue removed and irradiated breast volume >1000 cm3, while higher absolute volumes were found in patients with >26 cm posterior separation (58.0 cm3 vs 102.7 cm3; P = .07). No meaningful difference was observed in Dmax or radiation coverage (95% of the volume receiving 95% of the prescription dose) for patients with >26 cm posterior separation, >500 cm3 of breast tissue removed, or irradiated breast volume >1000 cm3. Conclusions: Radiation dosimetry plans for patients undergoing oncoplastic surgery were acceptable and no significant radiation or surgical advantage was gained in patients with more tissue removed. Our study stresses the importance of clear communication between surgeons and radiation oncologists about sufficient marking of the lumpectomy cavity, using practices that minimize the need for re-excisions and minimize lumpectomy cavity disruption during rearrangement.

Neoadjuvant Radiotherapy Facility Type Affects Anastomotic Complications After Esophagectomy.

BACKGROUND: Esophagectomy is a complex oncologic surgery that results in lower perioperative morbidity and mortality when performed in high-volume hospitals by experienced surgeons; however, limited data exists evaluating the importance of neoadjuvant radiotherapy delivery at high- versus low-volume centers. We sought to compare postoperative toxicity among patients treated with preoperative radiotherapy delivered at an academic medical center (AMC) versus community medical centers (CMC). METHODS: Consecutive patients undergoing esophagectomy for locally advanced esophageal or gastroesophageal junction (GEJ) cancer at an academic medical center between 2008 and 2018 were reviewed. Associations between patient factors and treatment-related toxicities were calculated in univariate (UVA) and multivariable analyses (MVA). RESULTS: One hundred forty-seven consecutive patients were identified: 89 CMC and 58 AMC. Median follow-up was 30 months (0.33-124 months). Most patients were male (86%) with adenocarcinoma (90%) located in the distal esophagus or GEJ (95%). Median radiation dose was 50.4 Gy between groups. Radiotherapy at CMCs resulted in higher rates of re-operation after esophagectomy (18% vs 7%, p = 0.055) and increased rates of anastomotic leak (38% vs 17%, p < 0.01). On MVA, radiation at a CMC remained predictive of anastomotic leak (OR 6.13, p < 0.01). CONCLUSION: Esophageal cancer patients receiving preoperative radiotherapy had higher rates of anastomotic leaks when radiotherapy was completed at a community medical center versus academic medical center. Explanations for these differences are uncertain but further exploratory analyses regarding dosimetry and radiation field size are warranted.

Treatment Tolerance of Cetuximab versus Alternative Chemotherapy Agents in Non-Cisplatin Candidates with Head and Neck Cancer Receiving Concurrent Chemoradiotherapy.

INTRODUCTION: Standard of care for radiosensitization in head and neck squamous cell carcinoma (HNSCC) is concurrent chemoradiotherapy (CCRT) with high-dose cisplatin. The optimal chemoradiation regimen for patients medically unfit for cisplatin is unclear. We compared our experience with concurrent cetuximab (CTX) versus other cytotoxic non-cisplatin agents. METHODS: We reviewed 53 patients between 2011 and 2017 with HNSCC treated with CCRT ineligible for cisplatin. Chemotherapy and radiotherapy treatment tolerance was evaluated in those receiving CTX versus non-CTX chemotherapy (NCC). Of the NCC regimens, the majority were carboplatin/paclitaxel and were dosed at an area under the curve (AUC) of 2 and 45-50 mg/m2, respectively. Standard radiation dosing was 70 Gray (Gy) in the definitive setting and 60-66 Gy in the postoperative setting. Patient characteristics and treatment toxicities were evaluated using categorical methods. RESULTS: Patients were well balanced overall including differences between performance status and the comorbidity score. NCC patients experienced more radiation treatment breaks (52.4% vs. 21.9%, p = 0.022), radiation delays >1 week (33.3% vs. 3.1%, p < 0.01), and chemotherapy dose-limiting toxicity (61.9% vs. 28.1%, p = 0.015) compared to CTX patients. Nutritional dependence on a PEG tube was more likely in the NCC cohort (52.4% vs. 22.6%, p = 0.027). CONCLUSION: Our results suggest decreased treatment tolerance in non-cisplatin cytotoxic chemotherapy compared to cetuximab. Further prospective study is needed to clarify optimal chemotherapy in patients unable to receive cisplatin.

Diagnostic accuracy of FNA to determine HPV status in HPV-associated oropharyngeal squamous cell carcinoma.

PURPOSE/OBJECTIVE(S): Accurate diagnosis of human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC) affects prognosis and can alter the treatment plan. We evaluated the diagnostic accuracy of FNA biopsies to determine malignancy and HPV status in OPSCC at our institution. METHODS: Pathology samples from consecutive patients with pathologically confirmed HPV-associated OPSCC who underwent FNA of a cervical lymph node during initial diagnostic work-up were retrospectively analyzed between November 2015 and August 2021. RESULTS: Initial FNA was diagnostic for malignancy in 109/148 (73.6%) patients and non-diagnostic in 39/148 (26.4%). P16 staining of FNAs positive for malignancy showed: 54/109 (49.5%) p16 positive, 6/109 (5.5%) p16 negative, 49/109 (45.0%) p16 indeterminate. In patients with an initial non-diagnostic sampling or p16 indeterminate, repeat FNA was performed in 30/88 (34.1%) patients. Of the 30 repeat FNAs: 23/30 (76.7%) were diagnostic of malignancy and 7/30 (23.3%) remained non-diagnostic for malignancy. Of the 23 repeat FNAs diagnostic of malignancy: 16/23 (69.6%) were p16 positive and 7/23 (30.4%) were p16 indeterminate. In summary, 88/148 (59.5%) initial FNAs and 14/30 (46.7%) of repeat FNAs were non-diagnostic of malignancy or p16 indeterminate. Final yield of FNA biopsies (initial and first repeat FNA) to diagnose malignancy and p16 status was 70/148 (47.3%). CONCLUSIONS: Fine needle aspirations of lymph nodes in patients with HPV-associated OPSCC are frequently non-diagnostic for malignancy or indeterminate for p16 status, requiring repeat FNA or biopsy of the primary site. This can potentially cause treatment delay and increase morbidity and cost to the patient.

Radiosensitivity of Breast Cancer Cells Is Dependent on the Organ Microenvironment.

Background: Distant metastasis is the leading risk factor of death in breast cancer patients, with lung and liver being commonly involved sites of distant seeding. Ongoing clinical trials are studying the benefit from additional local treatment to these metastatic sites with radiation therapy. However, little is known about the tissue-specific microenvironment and the modulating response to treatments due to limitations of traditional in vitro systems. By using biomatrix scaffolds (BMSs) to recreate the complex composition of extracellular matrices in normal organs, we chose to study the radiotherapy response with engineered breast cancer "metastases" in liver and lung organ-specific tissues. Methods: Liver and lung BMSs were prepared for tissue culture. Human breast cancer cell lines were passaged on normal tissue culture plates or tissue culture plates coated with Matrigel, liver BMSs, and lung BMSs. Clonogenic assays were performed to measure cell survival with varying doses of radiation. Reactive Oxygen Species (ROS) detection assay was used to measure ROS levels after 6 Gy irradiation to cancer cells. Results: The response of breast cell lines to varying doses of radiotherapy is affected by their in vitro acellular microenvironment. Breast cancer cells grown in liver BMSs were more radiosensitive than when grown in lung BMSs. ROS levels for breast cancer cells cultured in lung and liver BMSs were higher than that in plastic or in Matrigel plate cells, before and after radiotherapy, highlighting the interaction with surrounding tissue-specific growth factors and cytokines. ROSs in both lung and liver BMSs were significantly increased after radiotherapy delivery, suggesting these sites create prime environments for radiation-induced cell death. Conclusions: The therapeutic response of breast cancer metastases is dependent on the organ-specific microenvironment. The interaction between tissue microenvironment in these organs may identify sensitivity of therapeutic drug targets and radiation delivery for future studies.

Sarcopenia and Treatment Toxicity in Older Adults Undergoing Chemoradiation for Head and Neck Cancer: Identifying Factors to Predict Frailty.

This study was performed to identify treatment related toxicities in older adults undergoing concurrent chemoradiotherapy for head and neck cancer and nutritional and skeletal muscle measures that might identify frailty. Imaging analysis was done with the following skeletal muscle measurements: skeletal muscle index (SMI), skeletal muscle density (SMD), and skeletal muscle gauge (SMG). Patients were dichotomized by age into younger (<70 years old, 221 patients) and older age groups (≥70 years old, 51 patients). Low SMI was more common in older patients (86.7%) compared to younger patients (51.7%, p < 0.01), as were low SMD (57.8% vs. 37.3%, p = 0.012) and low SMG (76.1% vs. 44.2%, p < 0.01), despite having similar BMIs (27.3 kg/m2 versus 27.7 kg/m2, p = 0.71). Older patients were significantly more likely to experience chemotherapy toxicity than younger patients (54.9% versus 32.3%, p < 0.01). On multivariate analysis age (p < 0.01), current smoking status (p < 0.01), and low SMI (p < 0.01) remained as significant predictors for missed chemotherapy cycles or discontinuation. Older patients were more likely to require ≥5-day radiation breaks than younger patients (27.5% versus 8.6%, p < 0.01). On multivariate analysis, age (p < 0.01), low albumin status (p = 0.03), and low SMI (p = 0.04) were identified as predictors of prolonged radiation treatment breaks. Based on the results of our study, sarcopenia may be used as an additional marker for frailty alongside traditional performance status scales.

Stereotactic Body Radiation Therapy for Apical Lung Tumors: Dosimetric Analysis of the Brachial Plexus and Preliminary Clinical Outcomes.

PURPOSE: Dosimetric constraints of the brachial plexus have not yet been well-established for patients undergoing stereotactic body radiation therapy (SBRT). This study evaluated long-term experience with the treatment of early-stage apical lung tumors with SBRT and reports on dosimetric correlates of outcome. METHODS AND MATERIALS: Between 2009 and 2018, a total of 78 consecutive patients with 81 apical lung tumors underwent SBRT for T1-3N0 non-small cell lung cancer. Apical tumors were those with tumor epicenter superior to the aortic arch. The brachial plexus (BP) was anatomically contoured according to the Radiation Therapy Oncology Group atlas. Patient medical records were reviewed retrospectively to determine incidence of brachial plexus injury (BPI) and a normal tissue complication probability model was applied to the dosimetric data. RESULTS: Five patients (6.4%) reported neuropathic symptoms consistent with BPI and occurred a median 11.9 months after treatment (range, 5.2-28.1 months). Most common dose and fractionation in those developing BPI were 50 Gy in 5 fractions (4 patients). Symptoms consisted of pain in 2 patients (40.0%), numbness in the hand or axilla in 4 patients (80.0%), and ipsilateral hand weakness in 1 patient (20.0%). In the overall cohort the median BP Dmax (EQD23 Gy) was 5.13 Gy (range, 0.18-217.2 Gy) and in patients with BPI the median BP Dmax (EQD23 Gy) was 32.14 Gy (range, 13.4-99.9 Gy). The normal tissue complication probability model gave good fit with an area under the curve of 0.75 (odds ratio, 7.3; 95% confidence interval, 0.8-68.3) for BP Dmax (EQD23 Gy) threshold of 20 Gy. CONCLUSIONS: Significant variation exists in the dose delivered to the brachial plexus for patients treated by SBRT for apical lung tumors. The incidence of neuropathic symptoms in the post-SBRT setting was appreciable and prospective clinical correlation with dosimetric information should be used to develop evidence-based dose constraints.

Weekly cisplatin chemotherapy dosing versus triweekly chemotherapy with concurrent radiation for head and neck squamous cell carcinoma.

BACKGROUND: Triweekly high-dose cisplatin (100 mg/m2 ) with concurrent radiation therapy is the current standard of care in the definitive or appropriate postoperative setting in head and neck squamous cell carcinoma (HNSCC). We compared triweekly 100 mg/m2 with alternative weekly 40 mg/m2 and weekly <40 mg/m2 cisplatin regimens. METHODS: From 2011 to 2016, 163 patients received concurrent cisplatin and intensity-modulated radiotherapy for locally advanced HNSCC. Primary endpoints were overall survival (OS) and progression-free survival. RESULTS: Cisplatin weekly <40 mg/m2 showed inferior OS outcomes when compared to weekly 40 mg/m2 (P = 0.084) and triweekly 100 mg/m2 (P = 0.04) regimens. CONCLUSION: Our study displayed inferior outcomes with weekly cisplatin doses under 40 mg/m2 , suggesting the inferiority of low-dose weekly chemotherapy and the need for ongoing randomized trials to further explore 40 vs 100 mg/m2 chemotherapy regimens.