Received Radiation Therapy Research Articles

Effectiveness and toxicity of multidisciplinary treatment of head and neck cancer among people with HIV: Real-world evidence from a tertiary cancer center in Brazil.

e24139 Background: The incidence of head and neck squamous cell carcinoma (HNSCC) is rising among people with HIV (PWH). Previous studies have shown an increase in treatment-related toxicities in this population. This study aims to determine the demographics and treatment outcomes in this patient group at a tertiary cancer center in Brazil. Methods: HNSCC patients (pts) with HIV diagnosis treated at our institution between 2009 and 2022 were included. Medical charts were analyzed to extract clinical data. Log rank was used to compare survival estimates and stratified Cox regression model was used for univariate and multivariate analyses. Results: Our search identified 75 pts with HIV among 5956 pts with HNSCC. Median age at cancer diagnosis was 53 years (IQR 49-59.5), 80% were male and 82.7% had a smoking history. Most pts had an oropharynx primary tumor (38.7%) and locally advanced disease (80%), with T3 and T4 tumors in 55 pts (73.3%) and N+ in 48 pts (64.1%). A feeding tube (FT) was placed in 32% of pts before treatment. HIV viral load was detectable in 23 (30.7%) pts and 19 (25.3%) had a CD4 count of fewer than 200 cells/mm³, while 97.3% of the pts were on combination antiretroviral therapy at the time of HNSCC diagnosis. 26 pts were operated with curative intent and 20 pts received adjuvant therapy. In the total population, concurrent cisplatin-based chemoradiation (CCRT) was prescribed to 26 pts (34.7%) and 34 (45.3%) received radiotherapy (RT) alone. 65.4% of the pts in the CCRT group and 20.6% in the RT group were unable to complete treatment as prescribed, mostly due to toxicity. No pts with positive viral load or CD4 < 200 cells/mm³ were able to complete CCRT. Treatment toxicity led to hospitalization in 24% of pts and 7 pts needed FT placement. There were 8 deaths during treatment, 5 in pts with CD4 < 200 cells/mm³. Positive viral load was associated with CCRT interruption (p = 0.03) and a CD4 count of less than 200 cells/mm³ increased the risk of death during treatment (p = 0.02). Median overall survival (OS) was 31.7 months (IQR 14.6-53.7). Multivariate analysis did not show a statistically significant decrease in OS in pts with positive viral load or CD4 < 200 cells/mm³. Factors associated with worse OS on multivariate analysis were FT usage (HR = 2.91; 95% CI: 1.45-5.83) and Eastern Cooperative Oncology Group Performance Status (ECOG-PS) greater than 1 (HR = 3.26; 95% CI: 1.46-7.24). Conclusions: HNSCC treatment in PWH is associated with a high discontinuation rate, even in pts with antiviral therapy. High toxicity rates and deaths during treatment were observed. Positive viral load and low CD4 count were considered contributing factors. ECOG-PS and enteral feeding tube usage were independently associated with worse survival. The development of more tailored strategies in this population is needed to improve outcomes in patients with HNSCC and HIV.

A prospective phase II randomized clinical study of folic acid in the intervention of radiation esophagitis induced by concurrent chemoradiotherapy in lung cancer.

e20004 Background: To investigate the efficacy and safety of folic acid intervention in lung cancer patients with radiation esophagitis caused by concurrent chemoradiotherapy. Methods: It was a randomized, controlled, single-center clinical trial of 82 patients with stage N2~N3 lung cancer including SCLC and NSCLC were prospectively included. All patients were randomly divided into experimental and control group according to 1:1, and patients were required to receive radiation therapy for lung lesions and mediastinal metastatic lymph nodes (More than 2 cycles of chemotherapy were completed during the same period of radiotherapy or take targeted drugs at the same time, the cumulative radiation dose of chest lesions should exceed 40Gy). The experimental group took folic acid tablets 30mg/day orally at the beginning of radiotherapy until the end of radiotherapy, while the control group did not receive any drug intervention.When two groups appeared radiation esophagitis, the grading criteria for RTOG should be evaluated first, then according to the guidelines of symptomatic treatment.Esophageal toxicity was evaluated during radiotherapy, and improved RTOG and NCI-CTC ratings were performed weekly at the onset of radiation esophagitis and thereafter until 1 week after the end of radiotherapy. Results: The incidence of radiation esophagitis in the experimental group was low during the observation period, and the occurrence time of radiation esophagitis could be delayed in the experimental group, but there was no statistical significance between the two groups ( P=0.456). After folic acid intervention, the symptoms of pain and dysphagia of radiation esophagitis in the experimental group were significantly decreased, especially the RTOG grade and NCI-CTC improvement grade decreased significantly 2 weeks after the occurrence of radiation esophagitis( P=0.007, P=0.009). In the experimental group, it was found that the greater the change of hemoglobin before and after radiotherapy, the occurrence time of radiation esophagitis was about delayed, which was statistically significant(r=0.348, P=0.040).The correlation analysis of the control group showed that the change of body mass index was positively correlated with the onset time of radiation esophagitis(r=0.372, P=0.020);The lower the hemoglobin content after radiotherapy and the larger the hemoglobin difference before and after radiotherapy, the higher the highest incidence of radiation esophagitis(r= -0.454, P=0.004;r= -0.343, P=0.032). Conclusions: Oral folic acid can delay the onset of radiation esophagitis due to concurrent chemoradiotherapy and promote the recovery of radiation esophagitis to a certain extent,but can not interfere with the occurrence of radiation esophagitis.This trial is registered in Clinical Trials(NCT0529636). Clinical trial information: NCT0529636 .

A Case of Inoperable Advanced Papillary Thyroid Carcinoma Maintaining Long-term Stable Disease State after Palliative Aim Radiation Therapy Alone

The current standard of treatment for differentiated thyroid cancer is surgical resection followed by radioactive iodine therapy according to the recurrence risk. However, external beam radiotherapy may be recommended in limited cases where surgical resection is impossible or residual gross lesion remains or the aforementioned standard therapy is deemed insufficient in achieving local control. We report a case of 59 year old patient who presented with advanced papillary thyroid carcinoma of right neck but was unable to receive surgical resection due to underlying Eisenmenger syndrome. He received radiation therapy of 67.5 Gy in 30 fractions with palliative aim with no further treatment and has been maintaining long-term stable disease state for 38 months. Herein, we report a rare case of palliative aim radiation therapy alone for advanced papillary thyroid carcinoma with literature review.

Association of Radiation-Induced Acute Esophagitis With Dosimetric Parameters of Oesophagus in Breast Carcinoma Patients Receiving Supraclavicular Nodal Irradiation.

We conducted this investigation to ascertain the dosimetric properties such as the mean and maximum radiation dosage during radiotherapy as well as the extent of radiation exposure to the esophagus. These factors can potentially impact the development of esophagitis in breast cancer patients undergoing supraclavicular radiation. From January to June 2023, an observational study was conducted at Bangabandhu Sheikh Mujib Medical University in Bangladesh. The patients received radiation therapy (40.05 Gy in 15 parts) to the chest wall and supraclavicular node for three weeks. We were able to guess the following from the dose volume histogram (DVH) data: the length of the esophagus in the treatment area (i.e., the size of the esophagus that was visible on the planning CT scan), the maximum dose (Dmax), the mean dose (Dmean), and the volume of the 10Gy (V10Gy) and 20Gy (V20Gy) doses that were given to the esophagus. During radiotherapy, patients were checked on once a week, and the radiotherapy oncology group was used to evaluate and grade esophagitis Results: Patients with left-sided breast cancer showed a higher Dmean, Dmax, and length of the esophagus compared to those with right-sided breast cancer. Specifically, the Dmean was 6.7 (±2.1) Gy, the Dmax was 39.2 (±1.5) Gy, and the length of the esophagus was 6.1 (±1.2) Gy. Patients with left breast cancer had elevated V10Gy and V20Gy values for the esophagus, but the difference was not statistically significant. The incidence of V10Gy for right-sided breast cancer and left-sided breast cancer was 4.2% (±2.6%) and 19.8% (±9.2%), respectively. The V20Gy was 2.4% (±0.9%) for right-sided breast cancer and 13.09% (±5.0%) for left-sided breast cancer Conclusion: In conclusion, there is a strong association between the mean oesophageal dose and radiation to the left supraclavicular region following surgery in women with breast cancer and acute esophagitis. We can reduce esophageal toxicity by prescribing dose restrictions and performing precise delineation of the esophagus.

Rectal volume is correlated with interfractional positional shifts of the prostate gland in dogs receiving radiation therapy.

Variability in prostate gland positioning during RT for prostate tumors is a recognized challenge in both human and veterinary oncology. This retrospective study investigates the interfractional variability in prostate gland positioning in relation to rectal and bladder volumes in dogs undergoing radiation therapy (RT) for prostate tumors. The study tracked 10 dogs undergoing five RT sessions from February 2016 to November 2021, delivering a total of 25Gy each. Each dog underwent CT scans for treatment simulation, and cone-beam CT (CBCT) images were acquired before each RT. The focus was to analyze the positional shifts of the prostate gland concerning the volumes of the rectum and urinary bladder. The pelvic bones were used as the point of reference. The rectal and bladder volumes were measured before each RT, and shifts in the prostate gland position were calculated by comparing coordinates from planning CT and treatment session images. Findings revealed significant correlations between prostate positional shifts in the dorsal-ventral (repeated measures correlation coefficient of -0.58 [range 00.75-00.33]; P<.001) and cranial-caudal directions (repeated measures correlation coefficient [95%CI] 0.56 [range 0.31-0.74]; P<.001) and rectal volume, while no significant relationship was observed with bladder volume. Shifts in the lateral direction were not correlated with either organ's volume. This study highlights the importance of considering rectal volume in canine prostate tumor RT to minimize positional uncertainties. Maintaining consistent rectal volume may enhance the precision of prostate targeting, potentially influencing the safety of RT.

Abstract PS01-07: Impact of Race and Ethnicity on Recurrence Risk in Patients with Ductal Carcinoma in Situ Treated with Breast-Conserving Surgery

Abstract Background: Among women with invasive breast cancer, clinical presentation, tumor biology and survival vary by race and ethnicity. However, the impact of race and ethnicity on clinical presentation and recurrence risk in women with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS) has not been well studied. We sought to compare rates of recurrence in women with DCIS across racial and ethnic groups and identify factors associated with recurrence. Methods: Patients with DCIS treated with BCS from 1978 to 2016 at a single institution were identified. Patients were grouped and analyzed based on self-reported race and ethnicity as: Asian, Hispanic, non-Hispanic Black (Black), non-Hispanic White (White). Individuals with undefined ethnicity were classified by race, while those lacking both race and ethnicity data were excluded. Clinicopathologic characteristics were compared across racial and ethnic groups. The association of race and ethnicity on recurrence risk was analyzed using Kaplan–Meier methods, competing risk analysis and multivariable analysis. Results: Overall, 4207 cases were included, of which 6% (n= 261) were Asian, 9% (n = 358) Black, 5% (n = 226) Hispanic and 80% (n = 3362) White. Median age was 57 years (IQR 49, 67), 56% received radiotherapy (RT) and 26% received endocrine therapy. Black women with DCIS were older; Asian women were younger (median age: 60 vs 53 respectively, p &amp;lt; 0.001). Black women were more likely to have a clinical presentation (p = 0.006), and Black and Hispanic women were more likely to require ≥3 excisions (p = 0.006). The use of RT was most common among Hispanic women (p = 0.02). At a median follow-up of 8.8 years, 602 (14%) had local recurrence (LR) (315 [52%] DCIS; 284 [47%] invasive and 3 [ &amp;lt; 1%] unknown). The 10-year rate of LR was 15% and was lower in those treated with RT than without (11% vs 20%, respectively; p&amp;lt; 0.0001), despite those receiving RT having more high-risk characteristics. Rates of LR varied significantly by race and ethnicity, with the highest 10-year rate in Black women (25%) compared with Asian (11%), Hispanic (15%) and White (14%) women (p = 0.03). This statistically significant difference persisted among the no RT cohort (10-year rate: 31% [Black], 13% [Asian], 25% [Hispanic], 19% [White], p = 0.043), but did not reach significance in the RT cohort (21% [Black], 9% [Asian], 9% [Hispanic] and 11% [White], p = 0.3). Using competing risk analysis, the risk of invasive recurrence was similar or lower than DCIS recurrence in each racial group with or without RT. After adjusting for other factors on multivariable analysis, there remained a higher risk of LR among Black women (hazard ratio [HR] 1.48, 95% CI 1.12-1.95, p = 0.01). Older age (p &amp;lt; 0.001), radiologic presentation (p = 0.02), margins ≥ 2 mm (p &amp;lt; 0.001), the use of endocrine therapy (p &amp;lt; 0.001) and the use of RT (p &amp;lt; 0.001) were associated with lower rates of LR (Table). Sixteen women (0.4%) developed distant disease, with similar rates among Asian (0%), Black (0.8%), Hispanic (0.9%) and White (0.3%) women (p = 0.2). Conclusion: Compared with Asian, Hispanic and White women, Black women with DCIS had a significantly higher rate of LR after BCS, even after adjusting for known clinicopathologic risk factors. Rates of distant recurrence were low, and similar across racial groups. These higher rates of LR should be considered when making decisions about adjuvant therapy. Table. Factors associated with local recurrence in women with ductal carcinoma in situ treated with breast-conserving surgery. HR, hazard ratio; CI confidence interval; Ref, referent. Citation Format: Natália Polidorio, V. Morgan Jones, Varadan Sevilimedu, Monica Morrow, Kimberly Van Zee, Andrea Barrio. Impact of Race and Ethnicity on Recurrence Risk in Patients with Ductal Carcinoma in Situ Treated with Breast-Conserving Surgery [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS01-07.

Abstract PO1-22-03: Radiation Toxicity and Treatment Outcomes in Breast Cancer Patients with ATM Pathogenic and VUS Mutations: Implications for Personalized Therapy

Abstract Introduction: Previous studies have shown that ATM (ataxia-telangiectasia mutated) mutations may be associated with increased radiation sensitivity and altered treatment response. However, there is a limited understanding of the clinical implications and optimal management strategies for breast cancer patients with ATM mutations receiving radiotherapy (RT). The aim of our study is to assess the impact of ATM mutations on radiation response and treatment outcomes in breast cancer patients undergoing RT. Material and Methods: A total of 79 female patients diagnosed with breast cancer were included in the study, with 31 (39.3%) having pathogenic (P) and likely pathogenic (LP) variants (all of the variants were heterozygous) and 48 (60.8%) having VUS variants detected through whole ATM gene sequencing screening for patients in accordance with NCCN clinical practice guideline. Statistical analysis, including descriptive, graphical, and inferential methods, such as the Kolmogorov-Smirnov test, Mann-Whitney U Test, and Chi-square tests, was conducted using SPSS version 25.0 to evaluate the normal distribution of continuous variable scores and perform quantitative and qualitative comparisons between groups at a 95% confidence level (p &amp;lt; 0.05). Results: The median age of the patients was 44 years (range: 24-74), with 75% of them being 50 years old or younger .The rate of breast cancer in patients with VUS variants was significantly higher in those aged 50 and below compared to those with P/LP variants (83% vs. 61%, p=0.028). There was no statistically significant difference in clinical stage, tumour histological type, and molecular subtype classification based on ATM gene variant type (P/LP vs. VUS) among the patients (p&amp;gt;0.05), but the rate of high tumour grade was significantly higher in the VUS variant group (65% vs. 40%, p=0.034). The rate of patients who received RT was 87%, with 26 patients receiving radiation to the breast or chest wall and 43 patients receiving additional regional lymph node irradiation. There were no statistically significant differences in surgical and systemic treatment types and RT dose based on ATM gene variant type (P/LP vs. VUS) (p&amp;gt;0.05). Among the patients who received RT, 33 (48%) experienced early-stage skin reactions, and 15 (22%) experienced late-stage skin reactions according to Common Terminology Criteria for Adverse Events (CTCAE) v5. No Grade 3, 4 and 5 early and late toxicity were observed . The rate of early (83% vs. 23%; p&amp;lt; 0.001) and late (35% vs. 13%; p=0.029) skin reactions was significantly higher in the P/LP variant group compared to the VUS variant group. Grade I lymphedema was observed in 2 (2.5%) patients, 1 (3.2%) in the P/LP group and 1 (2.1%) in the VUS group (p&amp;gt;0.05). Among the 23 patients who underwent breast reconstruction, 1 (4%) had implant revision and 1 (4%) experienced implant loss, both of which were observed in the pathogenic variant group (p&amp;gt;0.05). Conclusion: Limited clinical data exists on RT toxicity in breast cancer patients with ATM gene mutations, and clear guidelines for decision-making are lacking. Our study revealed higher rates of acute and chronic skin reactions in the P/LP variant group, highlighting the need for further investigation into the impact of these variants on treatment outcomes and patient management. However, it is crucial to manage these reactions effectively and not allow them to hinder treatment. Additional research and interventions are warranted to better understand and address these reactions, aiming to enhance the overall treatment experience and outcomes for patients with ATM gene mutations. Citation Format: Evrim Tezcanli, Seda Eroz, Ugur Ozbek, Ahmet Yesilyurt, CIHAN URAS, Nuran Bese. Radiation Toxicity and Treatment Outcomes in Breast Cancer Patients with ATM Pathogenic and VUS Mutations: Implications for Personalized Therapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-22-03.

Abstract PO5-15-09: DNA damage induced necroptosis predicts response to radioimmunotherapy

Abstract Background: More than half of all cancer patients receive radiotherapy (RT) during their cancer experience. DNA damage induced by RT can initiate a pro-inflammatory immune response within the tumor microenvironment (TME), yet this response is not uniformly observed across all tumors. Mre11 is one of the first responders to double stranded breaks and coordinates the DNA damage response. Recent work in our lab reveals that Mre11 is required for cGAS mediated detection of cytoplasmic DNA, in turn activating STING to engage the type I interferon signaling pathway, downstream of which can activate ZBP1/RIPK3/MLKL mediated necroptosis. The purpose of this study is to determine if expression of the necroptotic pathway may predict whether breast tumors benefit from RT to overcome ICI resistance and induce systemic anti-tumor immunity in the form of an abscopal response. Methods: Four Trp53-/- Balb/c breast cancer syngeneic allograft models with low tumor mutational burden and resistance to dual ICI (anti-PD1 and anti-CTLA4, BioXcell) were used. Mice were implanted with bilateral tumors and randomly divided into four treatment cohorts: untreated, RT, ICI, or RT+ICI, where RT (8Gyx3) was administered to one tumor. Two lines exhibited abscopal responses to RT+ICI (i.e., “abscopal models”), whereas the other two did not (i.e., “non-abscopal models”). To identify gene expression patterns associated with abscopal responding breast tumors, we performed spatial transcriptomic analysis of tumors 10 days after initiating treatment using the GeoMx whole transcriptome assay targeting panCK+ tumor cells and tumor adjacent CD45+ immune cells (N &amp;gt;5 for each treatment group and tumor type). Unsupervised hierarchical clustering was performed to identify gene expression patterns across areas of interest. Genes selectively induced by RT+ICI in abscopal models that were not induced in non-abscopal models were identified using two-tailed t-test and FDR correction for multiple testing (FDR&amp;lt; 5%). DeSEQ2 and GSEA analysis were performed using publicly available mouse gene sets (Broad Institute). Results: The TME in untreated tumors in the abscopal models demonstrate upregulation in the B cell survival pathway and apoptotic pathways compared to untreated tumors in non-abscopal models. Hierarchical clustering of immune related genes in CD45+ segments of RT+ICI treated tumors exhibiting an abscopal response revealed a global shift in gene expression profiles after treatment. GSEA analysis of CD45+ segments from abscopal models shows that RT+ICI treatment results in enrichment of the interferon mediated signaling pathway including interferon alpha (p&amp;lt; 0.0001), interferon beta (p&amp;lt; 0.0001), type II interferon response (p&amp;lt; 0.0001), and antigen processing and presentation (p&amp;lt; 0.0001). In tumor cells of breast cancers demonstrating the abscopal response, Isg15 and Zbp1 are highly induced by RT+ICI. The necroptotic pathway, including Zbp1, Ripk3, and Mlkl, are significantly higher expressed in the panCK+ tumors known to demonstrate the abscopal response. Conclusion: Breast cancer models with an abscopal response to RT+ICI demonstrate higher expression of Isg15 and Zbp1, both of which are involved in secreted inflammatory signaling. The TME in these models have increased interferon signaling and antigen presentation in response to RT+ICI. The role of DNA damage induced necroptosis in generating an abscopal response in breast cancer warrants further investigation as a potential biomarker for response to RT+ICI combination therapy. Citation Format: Anna Goddard, Qinhong Wang, Minguk Cho, Lynn Lerner, Gaorav Gupta. DNA damage induced necroptosis predicts response to radioimmunotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-15-09.

Abstract PO3-02-06: Predictive Factors for adjuvant radiation use in patients &amp;gt;70 years with pT1N0 HR+ breast cancers

Abstract Introduction: In 2004 the CALGB 9343 study reported that women &amp;gt;70 years of age with pT1NO hormone receptor positive breast cancer received no meaningful benefit from breast irradiation following lumpectomy. Although there was a modest reduction in local recurrence, there was no improvement in rates of mastectomy for local recurrence, distant metastases, 5-year overall survival (OS) and breast cancer specific survival therefore concluding that it was reasonable to omit radiation therapy in this group. An update of the CALGB 9343 study in 2013 with 10-year follow-up came to the same conclusion. Previous analysis of the National Cancer Database (NCDB) and the SEER database showed, however, that the majority of women with these characteristics were still receiving radiation therapy. We conducted this retrospective analysis from NCDB to identify factors associated with the use of radiation in this population. Methods: We reviewed the NCDB database and collected records of all breast cancer patients aged &amp;gt;70 years, who had hormone positive (HR+), pT1N0 disease between the years of 2004-2019. They were separated into radiation and non-radiation cohorts and then stratified based on ethnicity, age groups, insurance status, income quartiles, education quartiles, areas of residence, tumor size, comorbidities, diagnosis to treatment time, treatment facility type and geographic location. We then compared mortality between the two cohorts and completed a multivariate analysis to determine the demographic and clinical factors associated with the likelihood of receiving radiation. SAS was used for analysis and p-value &amp;lt; 0.05 was deemed as statistically significant. Results: 147,611 patients met the criteria of age &amp;gt; 70, pT1N0, HR+ treated with surgical lumpectomy. The majority of them were white, aged 70-75y, had Medicare, were in higher education and income quartiles and lived in metro areas (Table 1). 57.9% of the total study population received radiation. The possibility of receiving radiation decreased as age increased beyond 75 years. Uninsured patients, Medicare patients, those with comorbities, higher educational status as well as those who lived 20+ miles away from their treatment facility and treated at urban centers in central or south Atlantic areas were less likely to receive radiation. Those treated at Comprehensive community cancer programs and middle Atlantic areas were more likely to receive radiation. The possibility of radiation also progressively increased with tumor size. However, there were no differences observed when stratified by race, income status or chemotherapy use (Table 2). We also noted a small overall survival advantage for the radiation cohort (HR 0.77, p-value &amp;lt; 0.0001) which could be explained by the fact that patients without comorbidities were more likely to receive radiation. Discussion: Our results provide a real-world estimate of radiation use in pT1N0 HR+ early-stage breast cancer in women &amp;gt; 70 years. The major predictors of radiation use included younger age, low co-morbidities, insurance and institutions providing care. Lack of awareness about recent updates or concern about local recurrence could be contributing to the continued use of radiation. Although there are minor differences when stratified by demographics, it is concerning that the overall trend of radiation use has not significantly decreased over time. Since there is currently no data to support the routine use of radiation in this patient group as evidenced by randomized controlled trials, it is prudent to avoid radiation. This approach would help reduce healthcare costs, patient inconvenience and associated morbidity. Table 1 Baseline characteristics Table 2 Factors affecting radiation use Citation Format: Suma Sri Chennapragada, Runhua Shi, Shivani Sharma, Gary Burton. Predictive Factors for adjuvant radiation use in patients &amp;gt;70 years with pT1N0 HR+ breast cancers [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-02-06.

Abstract PS14-05: Safety evaluation from the KEYNOTE-522 study of neoadjuvant pembrolizumab (or placebo) plus chemotherapy followed by adjuvant pembrolizumab (or placebo) in patients with early triple-negative breast cancer (TNBC)

Abstract Background: In KEYNOTE-522 (NCT03036488), neoadjuvant (neoadj) pembrolizumab (pembro) + chemotherapy (chemo) followed by adjuvant (adj) pembro led to statistically significant and clinically meaningful improvements in the primary endpoints, pCR and EFS, vs neoadj placebo (pbo) + chemo followed by adj pbo in patients (pts) with newly diagnosed, high-risk, early TNBC. In the safety population at preplanned interim analysis 4 (IA4), treatment-related AEs in the combined phases (neoadj + adj) occurred in 98.9% of pts with pembro + chemo/pembro and 99.7% of pts with pbo + chemo/pbo; immune-mediated AEs of any grade occurred in 33.5% and 11.3% of pts, respectively. We report additional safety findings, beyond the already reported safety results, on immune-mediated AEs and management in the combined phases from IA4 of KEYNOTE-522. Methods: Eligible pts were randomized 2:1 to receive neoadj pembro 200 mg or pbo Q3W + paclitaxel-carboplatin for 4 cycles and then doxorubicin or epirubicin + cyclophosphamide for 4 cycles. After definitive surgery, pts received radiation therapy as indicated + adj pembro 200 mg or pbo Q3W for up to 9 cycles. Safety was assessed in all randomized pts who received ≥1 dose, underwent surgery, or both. AEs were monitored throughout the study and for 30 d post-treatment (90 d for serious AEs). Results: At IA4 (data cut-off: March 23, 2021), median treatment duration was 13.3 (range, 0-21.9) mo with pembro + chemo/pembro (n = 783) and 13.6 (range, 0-19.8) mo with pbo + chemo/pbo (n = 389). Of 341 pts with immune-mediated AEs and infusion reactions in the pembro + chemo/pembro arm (most events occurred in neoadj phase), 224 had grade 1-2 events and 117 had grade 3–5 events. The most common immune-mediated AEs with pembro + chemo/pembro were hypothyroidism (15.1%) and severe skin reactions (5.7%); infusion reactions occurred in 18.0% of pts (table). Of 118 pts with hypothyroidism, median time to onset was 105 d (range, 7–510 d) and 106 were treated with thyroid replacement, suggesting an endocrine abnormality and need for continued thyroid replacement. Of 45 pts with severe skin reactions, median time to onset was 64 d (range, 4–479 d) and 28 were treated with corticosteroids. Of 141 pts with infusion reactions, median time to onset was 16 d (range, 1–458 d) and 85 were treated with corticosteroids. Other immune-mediated AEs of interest with pembro + chemo/pembro were adrenal insufficiency (2.6%), pneumonitis (2.2%), and hypophysitis (1.9%); most of these events were grade 2–3. All 20 pts with adrenal insufficiency were treated with hormone replacement. Of 17 pts with pneumonitis, median time to onset was 167 d (range, 22-537 d) and 12 were treated with corticosteroids; median episode duration was 92 d. Of 15 pts with hypophysitis, 14 were treated with corticosteroids. Conclusion: In pts with newly diagnosed, high-risk, early TNBC, neoadj pembro + chemo followed by adj pembro had a manageable safety profile that was generally consistent with the known safety profiles of pembro and the chemo regimens. Most immune-mediated AEs and infusion reactions were grade 1-2, manageable with treatment interruption, corticosteroids, and/or hormone replacement therapy, and did not result in treatment discontinuation. Together with the efficacy findings, our results support neoadj pembro + chemo followed by adj pembro as a standard of care regimen for these pts. Table Citation Format: Javier Cortés, Rebecca Dent, Lajos Pusztai, Heather McArthur, Sherko Kuemmel, Carsten Denkert, Yeon Hee Park, Rina Hui, Masato Takahashi, Carlos Barrios, Yalin Zhu, Xiaoli Zhang, Wilbur Pan, Vassiliki Karantza, Joyce O'Shaughnessy, Peter Schmid. Safety evaluation from the KEYNOTE-522 study of neoadjuvant pembrolizumab (or placebo) plus chemotherapy followed by adjuvant pembrolizumab (or placebo) in patients with early triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS14-05.

Abstract PO2-10-01: Discrimination, Trust, and Pain Outcomes Among Black Women with Early-Stage Breast Cancer After Mastectomy

Abstract BACKGROUND Differences in perception, assessment, communication, and management of pain contribute to racial/ethnic pain disparities in breast cancer (BC). We previously found that Black women (BW) reported higher pain severity and interference with life after breast surgery compared to White women after adjusting for type of surgery and other potential confounders. Racial/ethnic inequities persist despite prior trials to improve disparate pain outcomes. This is likely because multiple factors contribute to pain expression, and structural factors affect the ability to control pain adequately. Perceived discrimination is associated with mistrust of medical providers. These factors are known to affect clinical outcomes, but their impact on pain has been understudied. In this preliminary analysis, we examine medical discrimination, trust in physician, and pain outcomes among BW with early-stage breast cancer after mastectomy. METHODS We surveyed BW with stage 0-III breast cancer who had mastectomy &amp;lt; 2 years of study enrollment at Baylor St. Luke’s Medical Center or Harris Health Smith Clinic in Houston, TX. Participants completed a demographic survey as well as the Brief Pain Inventory (BPI), Discrimination in Medical Settings Scale (DMS), and Trust in Physician Scale (TPS). In the BPI, participants reported their pain severity (PS) on a 0-10 scale at its worst, least, and on average. They reported pain interference with life (PI) from 0-10, types of pain treatments, and % relief from pain treatments. DMS and TPS questions were assessed on 5-point Likert scale. We performed chart review to obtain baseline clinical data related to BC diagnosis and treatment and comorbidities. We summarized patients’ baseline demographic and clinical information using descriptive statistics. PI and DMS were scored as a mean of the total items of each survey. We created mean Trust and Mistrust scores using means of the TPS questions related to each category. RESULTS Of the 37 BW surveyed, 36 (97.3%) were non-Hispanic. 23 (62.2%) had HR+ BC, and 2 (6.7%) had HER2+ disease. 26 (70.3%) women received chemotherapy, 10 (27%) received radiation therapy, and 17 (45.9%) received endocrine therapy. 26 (70.3%) women had &amp;gt; 1 comorbidity; the mean (SD) number reported was 1.3 (1.1). Mean BMI was 30.9 (6.6). 10 (29.4%) women completed high school, and 8 (23.5%) completed some college. 19 (55.9%) had a household income &amp;lt; $25,000, and 11 (32.4%) had private health insurance. Mean worst PS was 4.2 (3.1), and mean average PS was 3.6 (2.9). Mean composite PI score was 2.7 (2.7). 11 (29.7%) women were taking opioids for pain, 17 (45.9%) were taking non-opioid analgesics, and 3 (8.1%) were receiving non-medication treatments. Mean % pain relief with treatment was 52.3% (38.3). Mean DMS score was 1.2 (0.6). Mean composite TPS Trust and Mistrust scores were 4.4 (0.7) and 1.8 (1.0), respectively. CONCLUSION BW may continue to experience pain requiring opioid and/or non-opioid analgesics up to 2 years following mastectomy. Study participants reported relatively low levels of discrimination and high levels of trust on average. We are currently enrolling additional participants in the Emory Healthcare System and Grady Memorial Hospital in Atlanta, GA. After enrolling at least 80 total patients, we will determine the association between DMS and pain outcomes among participants adjusting for demographic, socioeconomic, and clinical factors as well as assess TPS as a potential mediator in the causal pathway between DMS and PS. Citation Format: Demetria Smith-Graziani, Yichun Cao, Jeffrey Switchenko, Mothaffar Rimawi, Abenaa Brewster. Discrimination, Trust, and Pain Outcomes Among Black Women with Early-Stage Breast Cancer After Mastectomy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-10-01.

Abstract PO1-22-10: Long term outcomes of breast cancer patients with local recurrence after mastectomy undergoing immediate breast reconstruction: A retrospective multi-institutional study of 4153 cases

Abstract Background: The number of breast cancer patients in Japan undergoing immediate breast reconstruction (IBR) has increased and the postoperative follow-up period has been extended. This study was conducted to clarify the clinical aspects of and factors associated with local recurrence (LR) after IBR. Methods: This was a multicenter study which included 4153 early breast cancer patients who underwent IBR. Clinicopathological characteristics were examined and factors potentially contributing to LR were analyzed. Risk factors for LR were examined separately for non-invasive and invasive breast cancers. Results: The median follow-up period was 75 months. The 7-year LR rates were 2.1% and 4.3% for non-invasive and invasive cancers, respectively (p &amp;lt; 0.001). The proportions of LR detected by palpation, subjective symptoms, and ultrasonography were 40.0%, 27.3%, and 25.9%, respectively. Overall, 75.7% of LR were solitary, and 92.7% of these cases had no further recurrences during the observational period. Multivariate analysis of LR for invasive cancer showed that skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM), the presence of lymphovascular invasion, cancer at the surgical margin, and not receiving radiation therapy were factors related to LR. The 7-year overall survival rates of the patients with LR and non-LR of invasive cancers were 92.5% and 97.3%, respectively, (p=0.002). Conclusions: The rate of LR after IBR was acceptably low and IBR can thus be performed safely for early breast cancer patients. Invasive cancer, SSM/NSM, lymphovascular invasion, and/or cancer at the surgical margin should prompt awareness of the possibility of LR. Citation Format: Akiko Ogiya, Naomi Nagura, Ayaka Shimo, Hiroko Nogi, Kazutaka Narui, Hirohito Seki, Hiroki Mori, Shinsuke Sasada, Makoto Ishitobi, Naoto Kondo, Chikako Yamauchi, Kohei Akazawa, Tadahiko Shien. Long term outcomes of breast cancer patients with local recurrence after mastectomy undergoing immediate breast reconstruction: A retrospective multi-institutional study of 4153 cases [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-22-10.

Abstract PO5-08-04: Characteristics of breast cancer in carriers of pathogenic variant in ATM in a large academic health center

Abstract Background: Pathogenic variants (PVs) in ATM are associated with an increased risk of breast, pancreas, and other cancers. The clinical and pathological characteristics of ATM-associated breast cancers have not been well defined. Methods: Patients who underwent multigene panel testing between December 2012 and May 2023 and were identified to harbor ATM PVs were included in the study. We analyzed demographics, germline findings, histopathology, genomic recurrence score, and management of ATM PV carriers with breast cancer. Results: A total of 222 individuals were identified to have PVs in ATM, of whom 184 (83%) were female. The majority were Caucasian (n = 179, 81%) and of those, 22 (12%) had Ashkenazi Jewish ancestry. The median age at genetic testing was 52y, with a range of 20-90y. A total of 111 patients (50%) had a personal cancer diagnosis, the most common of which was breast cancer (n = 70; 63%). The median age at breast cancer diagnosis was 53y, with a range of 25-84y. The most common histopathology was invasive ductal carcinoma (74%), followed by DCIS (21%), and invasive lobular carcinoma (5%). The majority of patients had breast tumors with stage 2 or 3 (78%), grade 2 or 3 (92%), ER and/or PR positive (92%) and HER2 negative (70%). One patient had triple-negative breast cancer. Forty-four percent of breast cancers were less than two centimeters, 23% were lymph node-positive, and 29% had lymphovascular invasion. Thirty-eight percent of patients underwent bilateral mastectomy, 54% received radiation therapy, 40% received adjuvant chemotherapy, 24% received neoadjuvant chemotherapy, and 70% received hormonal therapy. Of the 15 breast cancers with known 21-gene recurrence scores, 47% were intermediate (11-26), 33% were high (&amp;gt;=26) and 20% were low (&amp;lt; =10). Other notable cancers observed were pancreas (n = 9), colorectal (n = 6), prostate (n = 5), uterine (n = 4), melanoma (n = 4), and thyroid (n = 4). Conclusion: Our study outlines the clinical and pathological characteristics of ATM-associated breast cancer in a large academic center. The majority of breast cancers were invasive ductal type, early stage, intermediate or high grade, and hormone receptor-positive with an intermediate or high recurrence score. Despite the early stage, a significant proportion of patients underwent bilateral mastectomy. Further studies are needed to better elucidate the unique characteristics of breast cancer in ATM PV carriers in order to provide tailored management guidelines for this population. Citation Format: Ujjwal Karki, Tara Rangarajan, Dana Zakalik. Characteristics of breast cancer in carriers of pathogenic variant in ATM in a large academic health center [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-08-04.

Abstract PO4-08-04: Comparison of Outcomes and Prognosis between BRCA Pathogenic Variant Carriers Undergoing Breast-Conserving Surgery versus Mastectomy for Breast Cancer

Abstract Introduction: While outcomes are similar following breast-conserving surgery (BCS) or mastectomy among patients with sporadic breast cancer, data are still controversial for germline BRCA pathogenic variant carriers. We previously compared outcome following BCS between BRCA pathogenic variant carriers and non-carriers, and reported higher ipsilateral breast recurrence and comparable prognosis in the carriers. The purpose of this current study was to compare outcomes among BRCA pathogenic variant carriers undergoing BCS versus mastectomy in long-term follow-up period. Methods: Women with a BRCA pathogenic variant and a stage 0-III breast cancer who underwent definitive surgery from 1987–2021 were retrospectively identified from institutional database. Factors including clinicopathologic information and treatment characteristics were identified. Subsequent local recurrence, regional recurrence, distant recurrence, contralateral breast cancer (CBC), breast cancer-specific survival (BCSS), and overall survival (OS) rates were compared between BCS and mastectomy using Kaplan-Meier method and log-rank test. The chi-square test and t-test were used to compare patient characteristics between the two groups. Results: A total of 232 BRCA mutation carriers with 257 cancers including 25 patients with synchronous bilateral breast cancer were identified. Surgical treatment included BCS for 82 cancers and mastectomy for 175 cancers including nipple-sparing mastectomy for 51 cancers. Patient age at surgery and cancer stage did not statistically differ between BCS and mastectomy groups. Comparing to patients choosing mastectomy, patients who underwent BCS were less likely to be aware of their genetic status before surgery and were more likely to receive radiation therapy (p &amp;lt; 0.001). Contralateral risk reducing mastectomy was performed in 22.5% (18/80) in the BCS group and 48.7% (74/152) in the mastectomy group (p &amp;lt; 0.001) concurrently or at any time after the first definitive surgery. Risk reducing salpingo-oophorectomy was performed in 40% (32/80) in the BCS group and 49% (75/152) in the mastectomy group (p = 0.17). At 7.5 years median follow-up, local recurrence rate was statistically higher in the BCS group than in the mastectomy group (20.0% in BSC vs. 4.6% in mastectomy, p = 0.043). In patients who underwent nipple-sparing mastectomy, 4.0% (2/51) had local subcutaneous recurrence and no nipple-areolar recurrence was observed. Median duration from the first definitive surgery to ipsilateral local recurrence was 10.0 years in the BCS group and 2.3 years in the mastectomy group. Regional lymph node recurrence (11.2% in BCS vs. 6.4% in mastectomy, p = 0.62), distant recurrence (13.7% vs. 9.2%, p = 0.84), CBC (15.0% vs. 8.6%, p = 0.70), BCSS (88.8% vs. 94.1%, p = 0.65) and OS (87.5% vs. 94.1%, p = 0.49) rates did not statistically differ between two groups. Conclusions: With 7.5 years median follow-up, higher local recurrence rate was observed in BCS than in mastectomy among BRCA pathogenic variant carriers. Our results found no statistical difference between BCS and mastectomy in regional recurrence, distant recurrence, CBC, and prognosis, indicating relatively higher risk in BCS. While BCS could be an option for BRCA pathogenic variant carriers willing to continue high-risk breast surveillance, shared decision making should be carefully performed based on the long-term local recurrence risk. Citation Format: Kumiko Kida, Junko Takei, Misato Suzuki, Megumi Okawa, Sakurako Kazama, Sakiko Kondo, Michiko Yamanaka, Atsushi Yoshida. Comparison of Outcomes and Prognosis between BRCA Pathogenic Variant Carriers Undergoing Breast-Conserving Surgery versus Mastectomy for Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-08-04.

Abstract PO3-22-03: Effect of Radiation Therapy on Survival Outcomes in Elderly ER/PR Positive AJCC Stage T1 Breast Cancer Patients

Abstract Background: The CALGB 9343 study in 2004 reported that women &amp;gt;70 years of age with pT1NO hormone receptor positive breast cancer received no meaningful benefit from breast irradiation following lumpectomy. The effectiveness of adjuvant radiation therapy in node negative, T1 tumor patients has been limited to institutional experiences with relatively lack of information in population-based studies. In this hospital-based study using National Cancer Data Base (NCDB) from 2004 to 2020, we report on adjuvant radiation therapy (XRT) usage and the survival outcomes in stage IA, IB, IC breast cancer patients who received XRT versus those who did not. Materials and Methods: Patients in the National Cancer Database (NCDB) who were registered between 2004 and 2019 and followed up to the end of 2020 were used in this research. We evaluated a cohort of 126,156 female breast cancer patients of age &amp;gt;= 70 years with the American Joint Committee on Cancer (AJCC) stage TIA, TIB, and TIC. All patients were ER/PR positive, received hormonal therapy, all patients were either white or black, were either privately or Medicare insured, received hormonal therapy, and patients were receipt of adjuvant chemotherapy or not. Radiation statuses were grouped as no radiation, radiation only and/or radiation with boost. Other adjusted variables included: age, race, Charlson comorbidity index, payer status, income, education, distance traveled, diagnosing/treating facility, location of treatment and treatment delay. SAS for Windows 9.4 was used for all data management and statistical analysis. Multivariate Cox regression was used to assess the effect of the XRT on overall survival while adjusting for other factors. All p-values &amp;lt; 0.05 or 95% Confidence Limits of Hazards Ratio (HR) does not include 1 were considered statistically significant. Results: Among 126,156 female breast cancer patients, the age distribution was 47.87%, 31.72%, and 20.4% for age group of 70-74, 75-79, 80 or older, respectively. Ninety-three percent of patients were white. 89% of patients were Medicare and 11% were privately insured at diagnosis. 21% of patient were with the Charlson Comorbidity index score 1 or above. 10.77%, 34.42% and 54.81% of patients were AJCC Stage T1A, T1B, and T1C respectively. 11.7% of patients received chemotherapy and 57.9% of patients received radiation therapy. 54.38%, 59.59%, and 57.59% of T1a, T1b, and T1c patients received the XRT, respectively. In univariate analysis, the XRT demonstrated a statistically significant increase of 10-year survival by 9.75%, 9.8%, and 12.6% in T1a, T1b, and T1c (all p &amp;lt; 0.0001) patients respectfully. In multivariate cox regression analysis, age was a predictor of survival outcome with a HR at 1.65, 3.02 for 75-79, and 80 or older as compared to 70-74 years old, respectively. In addition, compared to patients who traveled less than 20 miles, the HR were 0.90 for patients travelled more than 20 miles. AJCC stage was also associated the survival, a HR of 1.05 (95% CI: 1.01-1.186) for T1b, 1.16 (95% CI: 1.11 – 1.21) for T1c as compared for T1a. Adjusting for other factors, the usage of radiation reduced the risk of dying by 25% (HR=0.75, 95% CI: 0.73-0.77) when compared to no radiation therapy. Conclusion: The current study has demonstrated that more than 54% of these patients received radiation therapy. In univariate analysis, the benefit of adjuvant radiation therapy is more than 9.7% for T1a, T1b, and T1c on 10-year overall survival which is statistically significant. Adjusting for other factors, patients receiving radiation therapy in these elderly population have a 25% less chance of dying as compared to no radiation therapy regardless of AJCC Stage. A further propensity score matching method would help assess the effectiveness of radiation therapy on these patients’ population. A randomized prospective clinical trial would be better to define the precise benefit of adjuvant radiation therapy in this elderly population. Table 1 Patients Demographic, Social Economic and Clinical Characteristics XX- XX Table 3 Hazard Ratios estimate from Multivariate Cox Regression XX- XX Radiation Effect on Overall Survival of Elderly Breast Cancer Patients by Stage T1A, T1B, T1C XX- XX Citation Format: Runhua Shi, Gary Burton. Effect of Radiation Therapy on Survival Outcomes in Elderly ER/PR Positive AJCC Stage T1 Breast Cancer Patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-22-03.

Abstract PO5-08-05: Breast Cancer in PMS2 related Lynch Syndrome: evidence of a possible association?

Abstract Background: Lynch syndrome (LS) is a hereditary cancer predisposition syndrome caused by pathogenic variants (PVs) in mismatch repair genes, MLH1, MSH2, MSH6, and PMS2. LS is associated with increased risk of colorectal, and endometrial cancers but breast cancer risk is uncertain, with some studies suggesting MSH6 and PMS2 PVs may have a higher risk for breast cancer. Our study outlines the incidence and clinical characteristics of breast cancer in PMS2-related LS identified at a large academic center. Methods: Patients with PMS2 PVs identified between July 2009 and May 2023 were selected from a database at the Nancy and James Grosfeld Cancer Genetic Center at Beaumont Health. Data on demographics, genetic testing, cancer types, and breast cancer characteristics were retrospectively analyzed. Results: A total of 108 patients from 74 families were found to carry a pathogenic or likely pathogenic variant in PMS2, of whom the majority were female (75%) and Caucasian (85%). The median age at genetic testing was 52y (19 to 95y). The most common variant was c.137G &amp;gt; T (p.Ser46Ile), seen in 15 of 74 (20%) families. Forty-seven patients (46%) had a personal history of cancer, with a median age at diagnosis of 58y. Of these forty-seven patients, sixteen (34%) had multiple malignancies, including one patient with six separate cancers. The most common malignancies were breast (19; 40%), colon (16; 34%), followed by uterine cancer (7), pancreas (4), and prostate (3). The median age at breast cancer diagnosis was 53y, with a range of 41-78y. The most common histopathology was invasive ductal carcinoma (54%), followed by DCIS (31%), and invasive lobular carcinoma (15%). The majority of patients had breast tumors with stage 0 or 1 (75%), grade 2 (63%), ER-positive (92%), PR positive (67%), and HER2-negative (88%). One patient had triple-negative breast cancer. Sixty-seven percent of breast cancers were less than two centimeters, and 92% were lymph node-negative. Fifty-nine percent received radiation therapy and 53% received chemotherapy. Conclusion: Our study outlines the incidence and clinical characteristics of breast cancer in PMS2-related LS. Breast cancer was the most common malignancy in our cohort of PMS2 PV carriers, accounting for 40% of all cancers, supporting a possible association between PMS2 and breast cancer. The majority of PMS2-related breast cancers were invasive ductal type, early stage, intermediate grade, and hormone receptor-positive. Further studies with larger diverse cohorts of patients with LS are needed to better characterize a possible association in order to provide tailored breast cancer screening and management guidelines for this population. Citation Format: Ujjwal Karki, Tara Rangarajan, Dana Zakalik. Breast Cancer in PMS2 related Lynch Syndrome: evidence of a possible association? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-08-05.

Long-term outcome of primary clival chordomas: a single-center retrospective study with an emphasis on the timing of recurrences based on the primary treatment.

This study aimed to provide data on extended outcomes in primary clival chordomas, focusing on progression-free survival (PFS) and overall survival (OS). A retrospective single-center analysis was conducted on patients with clival chordoma treated between 1987 and 2022 using surgery, stereotactic radiosurgery, or proton radiation therapy (PRT). The study included 100 patients (median age 44 years, 51% male). Surgery was performed using the endoscopic endonasal approach in 71 patients (71%). Gross-total resection (GTR) or near-total resection (NTR) was attained in 39 patients (39%). Postoperatively, new cranial nerve deficits occurred in 7%, CSF leak in 4%, and meningitis in none of the patients. Radiation therapy was performed in 79 patients (79%), with PRT in 50 patients (50%) as the primary treatment. During the median follow-up period of 73 (interquartile range [IQR] 38-132) months, 41 recurrences (41%) and 31 deaths (31%) were confirmed. Patients with GTR/NTR had a median PFS of 41 (IQR 24-70) months. Patients with subtotal resection or biopsy had a median PFS of 38 (IQR 16-97) months. The median PFS of patients who received radiation therapy was 43 (IQR 26-86) months, while that of patients who did not receive radiation therapy was 18 (IQR 5-62) months. The Kaplan-Meier method showed that patients with GTR/NTR (p = 0.007) and those who received radiation therapy (p < 0.001) had longer PFS than their counterparts. The PFS rates following primary treatment at 5, 10, 15, and 20 years were 51%, 25%, 17%, and 7%, respectively. The OS rates at the same intervals were 84%, 60%, 42%, and 34%, respectively. Multivariate Cox regression analysis showed that age < 44 years (p = 0.02), greater extent of resection (EOR; p = 0.03), and radiation therapy (p < 0.001) were associated with lower recurrence rates. Another multivariate analysis showed that age < 44 years (p = 0.01), greater EOR (p = 0.04), and freedom from recurrence (p = 0.02) were associated with lower mortality rates. Regarding pathology data, brachyury was positive in 98%, pan-cytokeratin in 93%, epithelial membrane antigen in 85%, and S100 in 74%. No immunohistochemical markers were associated with recurrence. In this study, younger age, maximal safe resection, and radiation therapy were important factors for longer PFS in patients with primary clival chordomas. Preventing recurrences played a crucial role in achieving longer OS.

The Impact of Radiation Therapy in Patients with Systemic Sclerosis and Head and Neck Cancer

ObjectiveSystemic sclerosis (SSc) is considered a relative, or in some cases, absolute contraindication for radiation therapy for various cancers; however, radiation is standard of care and the best option for tumor control for locally advanced head and neck (H&N) cancer. We present a case series to document the post-radiation outcomes in patients with SSc and H&N cancer. MethodsPatients with SSc and H&N cancer treated with radiation were identified from two large Scleroderma Center research registries. Through chart review, we identified whether patients developed pre-determined acute and late side effects or changes in SSc activity from radiation. We further describe therapies used to prevent and treat radiation-induced fibrosis. ResultsThirteen patients with SSc who received radiation therapy for H&N cancer were included. Five-year survival was 54%. Nine patients (69%) developed local radiation-induced skin thickening and seven (54%) developed reduced neck range of motion. Two patients required long-term percutaneous endoscopic gastrostomy use due to radiation therapy complications. No patients required respiratory support related to radiation therapy. Regarding SSc disease activity among the patients with established SSc prior to radiation therapy, none experienced interstitial lung disease progression in the post-radiation period. Following radiation, one patient had worsening skin disease outside the radiation field, however, this patient was within the first year of SSc when progressive skin disease is expected. Treatment strategies to prevent radiation fibrosis included pentoxifylline, amifostine and vitamin E, while intravenous immunoglobulin (IVIG) was used to treat it. ConclusionWhile some patients with SSc who received radiation for H&N cancer developed localized skin thickening and reduced neck range of motion, systemic flares of SSc were uncommon. This observational study provides evidence to support the use of radiation therapy for H&N cancer in patients with SSc when radiation is the best treatment option.

A natural compound melatonin enhances the effects of Nimotuzumab via inhibiting EGFR in glioblastoma

Sleep disorders are prevalent and debilitating symptoms in primary brain tumor patients, notably those receiving radiation therapy. Nevertheless, the relationship between sleep disorders, melatonin - a circadian rhythm regulatory hormone, and gliomas is underexplored. Melatonin exhibits various biological functions, one of them being anti-tumor activity. In the context of gliomas, often overexpressing EGFR, the humanized monoclonal antibody Nimotuzumab targets this marker. Our research discovered that variations in circadian rhythm significantly influence tumor growth in mice through impacting melatonin secretion. Harnessing proteogenomic, we identified that melatonin could inhibit the phosphorylation of EGFR and its downstream effectors, key elements in angiogenesis and tumor progression. Building on structural simulations, we propose that melatonin may amplify Nimotuzumab's anti-glioma efficacy by inhibiting EGFR TK dimerization. This proposition was validated in our in vitro and in vivo studies where melatonin synergistically augmented cytotoxicity and apoptosis in Nimotuzumab-treated glioma cells. Thus, melatonin shows promise as a beneficial addition to Nimotuzumab treatment in glioma patients.

The effects of an integrated supportive programme on oral health in patients with head and neck cancer undergoing radiotherapy: A randomized controlled trial.

This study determines the effect of an integrated 12-month follow-up support programme on the oral health of patients with head and neck cancer (HNC) who received radiotherapy (RT). Participants were randomly assigned to an intervention group (n = 47) or a control group (n = 45). The intervention group received usual care and an integrated supportive programme, which included face-to-face education and telephone coaching. The control group received usual care. After a clinical dental examination, the prevalence of caries, gingival inflammation and plaque were registered. Oral health impact profile (OHIP)-14 and the WHO Oral Health Questionnaire for Adults were used to evaluate oral health in both groups. A total of 79 participants completed a 12-month follow-up. The intervention group had lower caries increment between baseline and the 12-month follow-up compared with controls, although this was not statistically significant. After 12 months, the intervention group had statistically significant better outcomes in the plaque index (p = 0.038) and the OHIP-14 (p = 0.002) than the control group. No statistically significant differences were found between the two groups concerning gingival index. However, the intervention group reported an overall better state of teeth (p = 0.034) and gums after 12 months (p = 0.042). The integrated supportive programme showed positive effects on improving oral health in patients with HNC regarding plaque control, the state of teeth and gums and oral health-related quality of life during the 12-month follow-up.