Cancer Treatment Setting Research Articles

Traditional and Complementary Medicine Use among Cancer Patients in Asian Countries: A Systematic Review and Meta-Analysis.

Globally, cancer patients frequently use T&CM during their treatment for various reasons. The primary concerns regarding the use of T&CM among cancer patients are the potential risks associated with interactions between pharmaceuticals and T&CM, as well as the risk of noncompliance with conventional cancer treatments. Despite the higher prevalence of T&CM use in Asia, driven by cultural, historical, and resource-related factors, no prior review has tried to estimate the prevalence and influencing factors of T&CM use and disclosure among cancer patients in this region. This study aims to examine the prevalence and disclosure rates of T&CM use among cancer patients in Asia to assess various factors influencing its use across different cancer treatment settings in Asia. Systematic research on T&CM use was conducted using four databases (PubMed, EMBASE, Web of Science, and CINAHAL) from inception to January 2023. Quality was assessed using the Appraisal Tool for Cross-Sectional Studies (AXIS). A random effects model was used to estimate the pooled prevalence of T&CM use, and data analysis was performed using Stata Version 16.0. Among the 4849 records retrieved, 41 eligible studies conducted in 14 Asian countries were included, involving a total of 14,976 participants. The pooled prevalence of T&CM use was 49.3%, ranging from 24.0% to 94.8%, and the disclosure rate of T&CM use was 38.2% (11.9% to 82.5%). The most commonly used T&CM modalities were herbal medicines and traditional medicine. Females were 22.0% more likely to use T&CM than males. A subgroup analysis revealed the highest prevalence of T&CM use was found in studies conducted in East Asia (62.4%) and those covered by both national and private insurance (55.8%). The disclosure rate of T&CM use to physicians remains low. Moreover, the factors influencing this disclosure are still insufficiently explored. Since the disclosure of T&CM use is a crucial indicator of patient safety and the quality of cancer treatment prognosis, future research should focus on identifying the determinants of non-disclosure.

(135) DYSORGASMIA IN A FEMALE PATIENT FOLLOWING TRAM RECONSTRUCTIVE SURGERY

Abstract Introduction Many women struggle with sexual dysfunction, either in desire, arousal, orgasm, and/or pain. Despite the incidence of dysorgasmia in the general population, there is a paucity of literature focusing on its causes and treatment, especially when attributed to medical conditions and surgery. Objective This case report describes an unusual presentation of post-orgasmic pain following breast reconstruction surgery using abdominal tissue. Methods A 73-year old woman presented with chronic orgasmic pain in the deep pelvic area following transverse rectus abdominal muscle (TRAM) flap reconstruction for a mastectomy in the setting of breast cancer treatment. The patient was diagnosed with ductal carcinoma breast cancer in 2011, where she received a lumpectomy with radiation. After 2 years, in 2013, she was diagnosed with a recurrence of breast cancer. She underwent a mastectomy with no complications, with a transverse rectus abdominal muscle flap reconstruction surgery conducted five days later. Following the TRAM reconstruction, the patient consistently began to observe pain with orgasm. Results Prior to this surgery, the patient had experienced normal sexual intercourse and orgasm throughout her life. The patient describes pain with orgasm associated with self-stimulation, manual stimulation, oral stimulation, and vaginal penetration. The patient describes the pain associated with orgasm as a “deep, dull pain” causing nausea and is often associated with abdominal spasms. The pain lasts 2-3 minutes following orgasm and is rated as a 5-6/10 on the pain scale. The pain is not associated with urinary incontinence, urinary fullness, or bowel dysfunction. Physical exam revealed a tense abdominal wall consistent with TRAM reconstruction, well healed incisions, a normal clitoris in terms of appearance and sensation and normal pelvic floor muscles. Conclusions An orgasm is a complex process which involves interplays between the clitoris, the glans pubis, and the sympathetic activation system. A four-phase model for orgasm has been explored, which separates the orgasm response into: desire (the urge to participate in sexual activities), arousal (increased genital blood flow and clitorial erection), orgasm (after the threshold for stimulation has been reached), and resolution. Dysorgasmia can be multifactorial, and while still unclear, etiologies include pelvic floor dysfunction and/or spasm. While the pathophysiology of how the pelvic floor is connected to orgasm is not exactly understood, it is theorized to be due to dysregulated coordination of pelvic floor muscles. A transverse rectus abdominis muscle (TRAM) flap is a common breast reconstructive procedure following mastectomy. The most common complications of a TRAM flap surgery are hernias/abdominal bulges, fat necrosis, and loco-regional occurance. Interestingly, TRAM surgeries have previously been associated with pelvic floor dysfunction in women due to an increase in abdominal pressure. Since the pelvic floor is tightly connected to the mechanism of an orgasm, it is possible that disruptions to the pelvic floor may lead to painful spasms during orgasms. This is also consistent with the patient’s sensation of abdominal “spasms” during/after orgasm. While not all TRAM surgeries cause dysorgasmia, this patient’s dysorgasmia may be postulated to be secondary to pelvic floor dysfunction. Disclosure No.

Knowledge, Attitude and Practice among Nurses Regarding Prevention of Central Line Associated Bloodstream Infection in Tertiary Care Hospital of Peshawar

Healthcare Associated Infections (HAIs), particularly Central Line-Associated Bloodstream Infections (CLABSIs), remain a significant global public health concern. CLABSIs, associated with catheter use, pose critical challenges in critical care and cancer treatment settings, necessitating evidence-based measures for prevention. Objective: To assess the knowledge, attitude and practice of nurses regarding prevention of central line associated bloodstream infection in tertiary care hospital of Peshawar. Methods: This conducted study possessed a cross sectional study design with a random sample of 173 nurses who were presently working or had worked in ICUs of the hospital. Data were collected through a self-administered questionnaire. Data analysis was performed on SPSS version 22.0. Results: 45% of nurses demonstrated good knowledge with mean score of 12.35 and standard deviation of ± 1.45, positive attitudes were observed in 74% with mean score of 33.7 and standard deviation of ±2.1 and good practices in 80% of participants with mean score of 40.5 and standard deviation of 1.45 observe. Conclusions: This study clearly indicated that majority of the nurses (54.9%) have poor knowledge regarding CLABSI. Despite of the poor knowledge level most nurses (74%) followed standard practice. Interestingly, greater number of nurses (85%) were found to have positive attitude towards CLABSI.

Incidental Coronary Arterial Calcification for Cardiovascular Risk Assessment in Men With Prostate Cancer Undergoing PET/CT Imaging

BackgroundCardiovascular (CV) disease is common among men with prostate cancer and the leading cause of death in this population. There is a need for CV risk assessment tools that can be easily implemented in the prostate cancer treatment setting. MethodsConsecutive patients who underwent positron emission tomography/computed tomography (PET/CT) for recurrent prostate cancer at a single institution from 2012 to 2017 were identified retrospectively. Clinical data and coronary calcification on nongated CT imaging were obtained. The primary outcome was major adverse CV event (MACE; myocardial infarction, coronary or peripheral revascularization, stroke, heart failure hospitalization, or all-cause mortality) occurring within 5 years of PET/CT. ResultsAmong 354 patients included in the study, there were 98 MACE events that occurred in 74 patients (21%). All-cause mortality was the most common MACE event (35%), followed by coronary revascularization/myocardial infarction (26%) and stroke (19%). Coronary calcification was predictive of MACE (HR = 1.9, 95% CI: 1.1-3.4, P = .03) using adjusted Kaplan-Meier analysis. As a comparator, the Framingham risk score was calculated for 198 patients (56%) with complete clinical and laboratory data available. In this subgroup, high baseline Framingham risk (corresponding to 10-year risk of CV disease > 20%) was not predictive of MACE. ConclusionsMACE was common (21%) in men with recurrent prostate cancer undergoing PET/CT over 5 years of follow-up. Incidental coronary calcification on PET/CT was associated with increased risk of MACE and may have utility as a CV risk predictor that is feasible to implement among all prostate cancer providers.

Abstract 16419: Assessing the Evidence Base of Cardiology-Specific Oncology Guideline Recommendations: Implications for Health Policy

Introduction: Oncology societies have been contributing guidelines/recommendations to the limited yet growing body of literature in cardio-oncology. Research Questions: What are the levels of evidence (LOE) and classes of recommendation (COR) for cardiology-specific recommendations produced by major oncology societies? Methods: We reviewed cardiology-specific recommendations published by the American Society of Clinical Oncology (ASCO), American Society of Hematology (ASoH), NCCN (National Comprehensive Cancer Network), and European Society of Cardiology (ESC). LOE and COR were noted for each recommendation. Results: The US oncologic societies have made 81 cardiac-specific recommendations (ASCO: 54 (67%); ASoH: 14 (17%); NCCN; 13 (16%) (Tables 1-3). For ASCO, 26 (48%) were COR 1, 23 (43%) COR 2, and 5 (9%) COR 3 supported by LOE A (9%), LOE B (39%), and LOE C (52%). For ASoH, 1(8%) was COR 1, 11(85%) COR 2, and 1(8%) COR 3 supported by LOE B (7%), and LOE C (93%). NCCN made 13 COR 2 recommendations and did not provide LOE classification. The most common recommendations addressed baseline (20%) and serial (24%) assessment, specific imaging modalities (9%), chemotherapy dosing (19%), and radiation therapy (20%). Most recommendations were unique without discrepant statements, but there were some redundancies. ESC produced 271 cardio-oncology recommendations (155 COR 1; 111 COR 2; 5 COR-3) with 3% LOE A, 21% LOE B, and 76% LOE C. The major areas for ESC recommendations included baseline (18%) and serial (33%) assessment, and medications (29%). Conclusions: Oncology and cardiology professional society guidelines have provided 352 cardiac related recommendations in the setting of cancer treatment and 73% have the lowest LOE. In this developing field with a limited evidence base, close collaboration between cardiologists and oncologists will be required to provide a cohesive set of recommendations for the cardiac issues associated with cancer treatment.

Cardiovascular Imaging in Contemporary Cardio-Oncology: A Scientific Statement From the American Heart Association.

Advances in cancer therapeutics have led to dramatic improvements in survival, now inclusive of nearly 20 million patients and rising. However, cardiovascular toxicities associated with specific cancer therapeutics adversely affect the outcomes of patients with cancer. Advances in cardiovascular imaging have solidified the critical role for robust methods for detecting, monitoring, and prognosticating cardiac risk among patients with cancer. However, decentralized evaluations have led to a lack of consensus on the optimal uses of imaging in contemporary cancer treatment (eg, immunotherapy, targeted, or biological therapy) settings. Similarly, available isolated preclinical and clinical studies have provided incomplete insights into the effectiveness of multiple modalities for cardiovascular imaging in cancer care. The aims of this scientific statement are to define the current state of evidence for cardiovascular imaging in the cancer treatment and survivorship settings and to propose novel methodological approaches to inform the optimal application of cardiovascular imaging in future clinical trials and registries. We also propose an evidence-based integrated approach to the use of cardiovascular imaging in routine clinical settings. This scientific statement summarizes and clarifies available evidence while providing guidance on the optimal uses of multimodality cardiovascular imaging in the era of emerging anticancer therapies.

‘It’s communication between people who are going through the same thing’: experiences of informal interactions in hospital cancer treatment settings

PurposeIn hospital settings, patients, visitors, and staff engage in many interactions outside formal clinical encounters. Whilst many of these may be inconsequential, others contribute significantly to how patients and their carers experience cancer and its treatment. This article aims to explore the experiences and significance of interactions that occur outside formal clinical encounters in hospital cancer treatment settings.MethodsSemi-structured interviews were conducted with cancer patients, carers, and staff recruited from two hospital sites and cancer support groups. Hermeneutic phenomenology informed lines of questioning and data analysis.ResultsThirty-one people participated in the study: 18 cancer patients, four carers, and nine staff members. The experiences of informal interactions were grouped into three themes: connecting, making sense, and enacting care. The participants described how these encounters allowed connection with others in the hospital spaces, facilitating a sense of belonging, normality, and self-worth. Through these interactions, individuals participated in making sense of their experiences, to better anticipate the decisions and challenges that might lie ahead. By connecting with other individuals, they cared for others and felt cared for themselves, and were able to learn from, teach, and support each other.ConclusionsOutside the confines of the clinical discourses participants negotiate terms of engagement, sharing of information, expertise, and their own personal stories that they may employ to contribute to the individuals around them. These interactions occur within a loose and evolving framework of social interactions, an ‘informal community’, in which cancer patients, carers, and staff members play active and meaningful roles.

Virtual nutrition services in oncology.

e13504 Background: In 2016, the National Academy of Sciences, Engineering and Medicine convened a workshop to examine challenges patients experience accessing specialized nutrition care in outpatient cancer treatment settings. Inadequate Registered Dietitian Nutritionist (RDN) staffing and reimbursement were identified as barriers to timely care. Staffing challenges at our three destination community cancer centers led to a backlogged queue of nutrition consults resulting in a ≥ 4-week wait time for an appointment. A quality improvement project to address delays in care for patients at risk for malnutrition, resulted in implementation of a hybrid model utilizing remote RDNs to provide virtual Medical Nutrition Therapy (MNT) to supplement onsite RDNs. Methods: After approved in June 2022, two remote RDNs were hired to provide virtual patient care. Nationwide recruitment allowed for hiring rare talent. A project team was created to assure we followed all regulatory guidelines related to licensing and billing. RDNs were individually licensed in 14 states to cover where ≥ 70% of our patients reside. System-wide criteria and licensure alerts for appointments were established between scheduling and nutrition leaders. The first patients were seen virtually on October 14, 2022, with units of service (uos) logged in 15-minute increments. Results: Appointments were tracked from October 14, 2022, through February 3, 2023. 69.2% of 302 scheduled appointments were successfully delivered virtually via telehealth platform with a mean of 1.7 uos. The main reasons for nonuse of the platform were no shows (52.7%) and the need to convert to a phone call (32.3%). The mean uos was significantly higher in new patients compared to returning patients (2.23 versus 1.53; p<0.001). Conclusions: A hybrid model of onsite and virtual care RDNs has potential to improve access to nutrition care. New patient appointments averaged > 30 minutes, and follow-ups averaged < 30 minutes. This may help inform future scheduling of virtual MNT appointments. This model may allow for recruitment from a wider pool of RDNs. It may also help avoid delays in care for patients at risk for malnutrition and gaps in their cancer treatment. [Table: see text]

Real-world study of bevacizumab treatment in patients with ovarian cancer: a Chinese single-institution study of 155 patients

ObjectiveThe purpose of this study was to retrospectively assess the pattern, compliance, efficacy and safety of bevacizumab in Chinese ovarian cancer patients.MethodsWe reviewed the clinicopathological data of patients with histologically confirmed epithelial ovarian cancer, fallopian tube cancer and primary peritoneal adenocarcinoma, who were diagnosed and treated at the Department of Gynecologic Oncology of Peking University Cancer Hospital between May 2012 and January 2022.ResultsA total of 155 patients were eventually enrolled in this study, with 77 as first-line chemotherapy (FL) and 78 as recurrence therapy (RT) among which 37 patients were platinum sensitive and 41 were platinum resistant. Among the 77 patients in the FL group, 35 received bevacizumab during neoadjuvant chemotherapy (NACT) alone (NT), 23 received bevacizumab during both neoadjuvant and first-line chemotherapy (NT + FL) and 19 received bevacizumab during first-line chemotherapy alone (FLA). Among the 43 patients of NT and NT + FL groups undergoing interval debulking surgery (IDS), 38(88.4%) patients achieved optimally debulking and 24 (55.8%) patients had no residual disease after IDS. The patients in the FL group had a median progression free survival (PFS) of 15(95%CI: 9.951–20.049) months, and the 12-month PFS was 61.7%. In the RT group, the overall response rate (ORR) was 53.8%. According to multivariate analysis, the patients' platinum sensitivity had a significant impact on the PFS in the RT group. 13(8.4%) patients discontinued bevacizumab due to toxicity. Seven patients were in the FL group while 4 patients were in the RT group. The most common adverse event associated with bevacizumab therapy was hypertension.ConclusionBevacizumab is effective and well-tolerated in the real world setting of ovarian cancer treatment. Adding bevacizumab to NACT is feasible and tolerable. Receiving the regimen containing bevacizumab in the last preoperative chemotherapy did not result in increased intraoperative bleeding of IDS. Platinum sensitivity is the most important factor affecting the effectiveness of bevacizumab in recurrent patients.

Efficacy of smartphone applications to help cancer patients quit smoking: Protocol of the Quit2Heal randomized controlled trial

Cigarette smoking is highly prevalent among cancer patients in the United States (US), with up to half of cancer patients smoking at the time of their initial cancer diagnosis. However, evidence-based cessation programs are rarely implemented in oncology care, and smoking is not consistently treated in cancer treatment settings. Consequently, there is an urgent need for accessible and efficacious cessation treatments that are uniquely tailored to the needs of cancer patients. Here we describe the design and implementation of a randomized controlled trial (RCT) testing the efficacy of a smartphone app (Quit2Heal) versus a US Clinical Practice Guidelines-based app (QuitGuide) for smoking cessation among a planned sample of 422 cancer patients. Quit2Heal is designed to address cancer-related shame, stigma, depression, anxiety, and knowledge about the consequences of smoking/quitting. Quit2Heal is based on the principles of Acceptance and Commitment Therapy, a behavioral therapy that teaches skills for accepting cravings to smoke without smoking, values-driven motivation to quit, and preventing relapse. The primary aim of the RCT is to determine whether Quit2Heal has significantly higher self-reported 30-day point prevalence abstinence at 12 months relative to QuitGuide. The trial will also determine whether Quit2Heal's effect on cessation is (1) mediated by improvements in cancer-related shame, stigma, depression, anxiety, and knowledge about the consequences of smoking/quitting; and (2) moderated by baseline factors (e.g., cancer type, stage, time since diagnosis). If successful, Quit2Heal will offer a more efficacious, broadly scalable smoking cessation treatment that could be implemented alongside existing oncology care, thereby improving cancer outcomes.

Abstract 2642: BL-B01D1, a novel EGFR×HER3-targeting ADC, demonstrates robust anti-tumor efficacy in preclinical evaluation

Abstract EGFR and HER3, members of the human epidermal growth factor receptor (ErbB) family, are targeted in cancer therapy due to their over-expression and pathway dependence in common human epithelial carcinoma tumors. To develop a promising therapeutic anti-tumor agent, we generated BL-B01D1, an EGFR×HER3-targeting ADC, which can bind to EGFR and/or HER3 positive cells and is expected to be superior to anti-EGFR and anti-HER3 ADCs. It is comprised of a bispecific antibody against EGFR/HER3 (SI-B001), a cathepsin B cleavable linker, and a novel topoisomerase I inhibitor agent (Ed-04), which is a derivative of the alkaloid camptothecin, driving cell cycle arrest at the S phase and subsequent apoptosis. BL-B01D1 achieves a high drug-to-antibody-ratio (DAR=8) with a highly stable linker. The pharmacological potential of this ADC was evaluated in comparison to its parental single antigen-targeting ADCs in xenograft models composed of either the human colorectal cancer cell line SW620 or pancreatic cancer cell line BxPC3. The tumor inhibition activity of BL-B01D1 was compared with ADCs prepared from each parental anti-EGFR or anti-HER3 mAb conjugated with the same linker and payload. The bispecific ADC, BL-B01D1 exhibited stronger tumor inhibition capacity than the anti-EGFR ADC and the anti-HER3 ADC separately. The preclinical studies suggest BL-B01D1, as an EGFR×HER3-targeting ADC, might be a promising novel agent with activity toward a broad range of human cancers. The clinical phase I has been progressing and the available data exhibit excellent efficacy but low levels of targeted toxicity in the non-small cell lung cancer (NSCLC) treatment setting. Overall, these data suggest BL-B01D1 has potential to serve as a novel, efficacious therapeutic agent for NSCLC with similar therapeutic impact as DS-8201 has in breast cancer treatment. Citation Format: Weili Wan, Shuwen Zhao, Shi Zhuo, Yong Zhang, Lan Chen, Gangrui Li, Blair Renshaw, Jahan Salar Khalili, Sa Xiao, Yi Zhu. BL-B01D1, a novel EGFR×HER3-targeting ADC, demonstrates robust anti-tumor efficacy in preclinical evaluation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2642.

CDK4/6 Inhibitors—Overcoming Endocrine Resistance Is the Standard in Patients with Hormone Receptor-Positive Breast Cancer

Tamoxifen and aromatase inhibitors can be considered as some of the first targeted therapies. For the past 30 years, they were the endocrine treatment standard in the advanced and early breast cancer setting. CDK4/6 inhibitors, however, are the first substances in almost two decades to broadly improve the therapeutic landscape of hormone receptor-positive breast cancer patients for the upcoming years. This review is designed to discuss the recent history, current role, future directions and opportunities of this substance class. The CDK4/6 inhibitors abemaciclib, dalpiciclib, palbociclib and ribociclib have all demonstrated a statistically significant improvement in progression-free survival in advanced disease. However, to date, abemaciclib and ribociclib are the only CDK4/6 inhibitors to have shown an improvement in overall survival in patients with metastatic breast cancer. Moreover, abemaciclib is the first CDK4/6 inhibitor to also reduce the risk of recurrence in those with early-stage disease. Further CDK inhibitors, treatment combinations with other drugs and different therapy sequences are in development. Achieving significant improvements in survival rates in the advanced and early breast cancer treatment setting, CDK4/6 inhibitors have set a new standard of care for patients with advanced breast cancer. It remains important to better understand resistance mechanisms to be able to develop novel substances and treatment sequences.

Molecular testing to deliver personalized chemotherapy recommendations: risking over and undertreatment

BackgroundIn the adjuvant setting of cancer treatment, de-escalation strategies have the goal of omitting or minimizing treatment in patients, without compromising outcomes. Historically, eligibility for adjuvant treatment solely relied on the patient’s clinical and tumor’s pathological characteristics. At the turn of the century, based on new biological understanding, molecular-based strategies were tested and sometimes implemented.Main bodyHowever, we illustrate how molecularly based de-escalation strategies may paradoxically lead to overtreatment. This may happen when the novel approach is tested in lieu of standard management and may not yield the same results when being implemented in addition to usual practice. In the DYNAMIC trial, adjuvant chemotherapy decision in stage II colon cancer was compared between a circulating tumor DNA (ctDNA)-based approach and the standard care. We show this may result in more patients receiving oxaliplatin-based chemotherapy and may expose a similar proportion of patients to chemotherapy if the novel strategy is implemented in addition to usual practice. The other potential risk is undertreatment. We provide an illustration of early breast cancer, where the decision of adjuvant chemotherapy based on the gene expression signature MammaPrint may lead to inferior outcomes as compared with the clinico-pathologic strategy. This may also happen when non-inferiority designs have large margins. Among solutions, it should be acknowledged that clinico-pathological features, like T4 in colon cancer, may not be abandoned and replaced by novel strategies in real-life practice. Therefore, novel strategies should be tested in addition to standard of care, and not in lieu of. Second, de-escalation trials should focus on the settings where the standard of care has a widespread agreement. This would avoid the risk of testing non-inferiority against an ineffective therapy, which guarantees successes without providing informative data.ConclusionSimply because a molecular test is rational does not mean it can improve patient outcomes. Here, we highlight how molecular test-based strategies may result in either overtreatment or undertreatment. In the rapidly evolving field of medicine, where technological advances may be transformative, our piece highlights scientific pitfalls to be aware of when considering running such trials or before implementing novel strategies in daily practice.

Physician Rated Cosmesis and Patient Reported Outcomes after Concomitant Boost (CB) vs. Sequential Boost (SB) for Adjuvant Treatment of Breast Cancer: A Prospective Randomized Study

<h3>Purpose/Objective(s)</h3> The aim of the current study was to compare toxicity, cosmesis and patient reported outcomes after sequential radiation therapy boost vs. concomitant boost in the adjuvant setting of breast cancer treatment. <h3>Materials/Methods</h3> One hundred and forty-five breast cancer patients who underwent breast conserving surgery and were candidates for tumor bed boost following whole breast irradiation (WBI) were randomized to receive either concomitant boost (CB) (n=71) or sequential boost (SB) (n=74). All patients received WBI to a total dose of 40.05 Gy/15 F/3 weeks. Patients in the SB arm received 10 Gy/5 F / 1 week to the boost volume following WBI. Patients in the CB arm received 7.95 Gy/15 F/3 weeks to the boost volume concomitant with the WBI. All treatments were carried out using 3D conformal radiation therapy. Physicians rated cosmesis prior to starting radiation and at 6 and 12 months after end of treatment. All patients filled a validated quality of Life questionnaire 12 months after end of treatment. <h3>Results</h3> Median follow-up 30 months (range, 18-48). G III or higher acute skin toxicity was observed in 12 (16.4%) patients in the SB arm and in 4 (6.3%) patients in the CB arm (p 0.042). GII or higher late skin toxicity developed in 4 (5.4%) patients in the SB arm and in 1 (1.4%) patient in the CB arm (p 0.18). GII subcutaneous fibrosis was observed in 3 (4%) patients in the SB arm and in none of the patients in the CB arm. Prior to radiation treatment, 50 (67.5%) patients had Excellent/good cosmesis in the SB arm vs. 47 (66.2%) patients in the CB arm (p 0.59). At 6 months after radiation, 44 (59.4%) patients had Excellent/good cosmesis in the SB arm vs. 40 (56.3%) patients in the CB arm (p 0.83). At 12 months after radiation, 50 (67.5%) patients in the SB arm had Excellent/good cosmesis vs 42 (59.2%) patients in the CB arm (p 0.57). twelve months after radiation, 50 (78.1%) patients in the SB arm reported very satisfied/satisfied with their cosmetic outcomes compared to 44 (72.1%) patients in the CB arm (p 0.43). <h3>Conclusion</h3> Concomitant boost radiation therapy is non-inferior to sequential boost in terms of late toxicity, cosmesis and patient satisfaction with slightly more favorable outcome in the acute toxicity and shorter overall treatment time.

Promoting positive physical activity behaviors for children and adolescents undergoing acute cancer treatment: Development of the CanMOVE intervention using the Behavior Change Wheel.

BackgroundIncreasing participation in physical activity has the potential to improve outcomes for children and adolescents with cancer during treatment and into survivorship. The aim of this study is to outline the theoretical process behind development of CanMOVE, a behavior change intervention designed to increase physical activity for children and adolescents with cancer.Study designThis study followed a theoretical design process consistent with the Behavior Change Wheel to inform the design of a complex intervention.Materials and methodsThe three stages of the Behavior Change Wheel intervention design process include: (1) understanding physical activity behavior within the pediatric cancer setting, (2) identifying potential intervention functions, and (3) identifying appropriate behavior change and implementation strategies. Qualitative and behavior change literature relevant to the pediatric cancer treatment setting were used to inform each stage.ResultsAn individualized and flexible approach to physical activity promotion that considers intrinsic factors specific to the child/adolescent and their environment is required. Fifteen behavioral change strategies were identified to form the intervention components of CanMOVE. Implementation strategies were identified to build motivation, opportunity and capacity toward increasing physical activity behaviors. Key intervention components of CanMOVE include standardized assessment and monitoring (physical activity, physical function, and health-related quality of life), provision of an activity monitor to both child/adolescent and parent, and one-on-one capacity building sessions with a healthcare professional. Capacity building sessions include education, goal setting, an active supervised physical activity session, barrier identification and problem solving, and action planning.ConclusionCanMOVE is a novel approach to physical activity promotion in the pediatric cancer treatment setting. The use of a theoretical intervention design process will aid evaluation and replication of CanMOVE when it is assessed for feasibility in a clinical setting. The design process utilized here can be used as a guide for future intervention development.

The capillary lobule variant of radiation-associated angiosarcoma in the setting of breast cancer: A diagnostic pitfall.

Post-radiation angiosarcoma is an iatrogenic event seen in the setting of breast cancer treatment. Histopathologically, there are morphologic variants of angiosarcoma that mimic benign entities, including the capillary lobule variant of post-radiation angiosarcoma. We present the largest case series to date of this histopathologic variant of post-radiation angiosarcoma. Cases of the capillary lobule variant of post-radiation angiosarcoma from institutional/consultation archives from 2008 to June 2022 were reviewed. For inclusion, tumors had to occur in irradiated skin and exhibit a multi-lobular proliferation of tightly packed capillary-like vessels, as previously described in this variant. Prior ancillary studies were also reviewed. Eight cases met the criteria. All occurred in women treated with radiation for breast cancer (median age 75 years). All cases had similar findings, including a multi-lobular proliferation of tightly packed vessels, infiltrative cords, and atypical single endothelial cells. A conventional angiosarcoma pattern was also seen in five cases. All cases tested were positive for vascular markers (CD31, CD34, and/or ERG) and MYC. MYC amplification was shown by FISH in all cases tested. Smooth muscle actin (SMA) was positive in pericytes in the capillary lobules in all five cases tested and areas of conventional angiosarcoma in two of three cases. The capillary lobule variant of angiosarcoma is a rare and therefore potentially under-recognized variant of post-radiation angiosarcoma. The lobular architecture and SMA positivity may mimic benign vascular proliferations. Careful attention to histopathologic features and ancillary tests may facilitate accurate diagnosis.

Breast Cancer and the Cardiovascular Disease: A Narrative Review.

Breast cancer is the most common malignancy affecting females worldwide and is also among the top causes of all cancer-related deaths. Cardiovascular disease (CVD) is known to have the highest rate of mortality in women. There are several risk factors for both CVD and breast cancer that overlap, such as diet, smoking, and obesity, and also the current breast cancer treatment has a significant detrimental effect on cardiovascular health in general. Patients with exposure to potentially cardiotoxic treatments, including anthracyclines, trastuzumab, and radiation therapy, are more likely to develop CVD than non-cancer controls. Early detection and treatment may reduce the risk of the development of cardiac morbidity and mortality and would increase the number of breast cancer survivors. This article provides a comprehensive overview of breast cancer, identifies shared risk factors among breast cancer and CVD, and the cardiotoxic effects of therapy. It also reviews possible prevention and treatment of CVD in breast cancer patients and reviews literature about chemoprevention of cardiac disease in the setting of breast cancer treatment.

P-56 Estimating endpoint correlation between surrogate measures and overall survival using reconstructed survival data: Case studies from adjuvant and metastatic gastric cancer trials

Validation of intermediate endpoints such as disease-free survival (DFS) and progression-free survival (PFS) as surrogate predictors for overall survival (OS) in randomized controlled trials (RCTs) requires establishing their association at the individual-level. In the absence of individual-level patient data (IPD), this study developed an analytical framework to estimate this association between DFS/PFS and OS using reported Kaplan-Meier (KM) curves from the RCTs and demonstrated its predictive performance in adjuvant and metastatic gastric cancer (GC) treatment settings. Assuming a three-state illness-death model for cancer survival, we developed a linear optimization model to elicit the underlying pre-progression death probability as well as post-progression survival (PPS) distribution using pseudo-patient level DFS/PFS and OS data reconstructed from the published KM curves. In the adjuvant setting, pre-progression death probability was bounded below by the cure rates which were estimated by fitting mixture cure models (MCMs) to the DFS data. In the MCMs, time-to-event outcomes for the uncured subpopulation were modeled using parametric survival functions suggested by National Institute for Health and Care Excellence (NICE) and non-disease-related mortality rates were derived from the age- and sex-adjusted local life-table data from World Health Organization. Reconstructed DFS/PFS distributions were extrapolated via parametric- and spline-based models suggested by NICE and adjusted with estimated background mortality rates whereas elicited PPS distributions were extrapolated assuming constant hazard rate over time. Estimated pre-progression death probabilities and modeled DFS/PFS/PPS distributions governed a Monte-Carlo simulation framework which generated paired pseudo pre- and post-progression data to predict Spearman’s rank and Pearson’s product moment correlation coefficients. Model performance was tested on two correlation meta-analyses in GC (14 RCTs with 3371 patients on adjuvant chemotherapy; 20 RCTs with 4069 patients on metastatic treatments) published in 2013 by the GASTRIC group. For each test case, model-predicted OS rates and Spearman rank correlation coefficients were compared against their reported counterparts and corresponding 95% CIs. Predicted OS curves laid within the 95% CIs of the reported OS KM-curves 96% and 100% of the time in the adjuvant and metastatic setting, respectively, where the average deviation between the restricted mean survival times under the model-predicted OS curves and the statistically best-fitting OS curves to the reported data was < 1% in both settings. Average deviation between the estimated and reported Spearman rank correlation coefficients was no more than 0.01 (reported: 0.97 [95% CI:0.97-0.98] vs. predicted: 0.96 [95% CI:0.96-0.96]) and 0.13 (reported: 0.85 [95% CI:0.85-0.85] vs. predicted: 0.72 [95% CI:0.71-0.72]) in both settings. Predicted Pearson correlation coefficients were 0.95 [95% CI:0.95-0.95] and 0.94 [95% CI:0.94-0.95] in the adjuvant and metastatic setting, respectively. Our study offers a useful approach for an indirect endpoint correlation assessment in the absence of IPD. Results indicate the model to be precise in adjuvant but conservative in metastatic GC setting which should be approached with caution due to independent simulation of paired DFS/PFS and PPS durations from the illness-death model and the lack of data-driven lower bounds on pre-progression death probability in the metastatic setting.

Incorporating mediation-based interventions at an academic cancer center: A six-step process.

e18662 Background: A growing body of evidence, including NCCN guidelines for distress management in oncology, supports the use of meditation-based interventions (MBI) in cancer care. However, MBI are generally delivered outside of the cancer treatment setting, with no integration between meditation instructors and the oncology care team. Further, there have been no studies to evaluate implementation of this evidence-based practice into routine cancer care. We report on the implementation process for establishing an integrated MBI program at an NCI-designated comprehensive cancer center. Methods: Guided by the Consolidated Framework for Implementation Research (CFIR), we developed a discrete MBI program as a strategy to implement MBI in our cancer center. Program components included 1) identifying champions and key stakeholders; 2) engaging with patient navigators and patient advocates; 3) partnering with cancer center leadership to gain infrastructure support; 4) establishing a meditation-focused program to increase acceptability amongst providers and patients; 5) launching an IRB-approved study to measure study outcomes; 6) leveraging social media, patient newsletters, and other institutional communication modes to increase awareness. We used the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework to define the outcome measures including reach (number of patients who attended an MBI session), adoption (number of providers who referred patients to MBI and number of patients who attended &gt; 1 MBI session), and implementation (feasibility and acceptability). Results: An MBI program has been successfully established within an NCI-designated comprehensive cancer and has received enthusiastic support from oncology providers, research nurses, as well as patient advocate groups. The intervention is delivered three times a week in 30 min sessions via videoconferencing. At the end of each session patients are encouraged to complete a short online survey about their experience. The first class has been established and enrolment is ongoing. Conclusions: Given the high prevalence of psychosocial distress in a rapidly expanding global cancer population, implementation of strategies to integrate psychosocial interventions, such as meditation, into routine care is critical. Well-defined MBI programs such as this can overcome the misperception that MBIs are difficult to implement in cancer centers and support the successful implementation of MBIs within cancer programs. Adoption of this evidence-based strategy can positively impact patient psychological resilience.

Recent Advances in the Development of Non-PIKKs Targeting Small Molecule Inhibitors of DNA Double-Strand Break Repair.

The vast majority of cancer patients receive DNA-damaging drugs or ionizing radiation (IR) during their course of treatment, yet the efficacy of these therapies is tempered by DNA repair and DNA damage response (DDR) pathways. Aberrations in DNA repair and the DDR are observed in many cancer subtypes and can promote de novo carcinogenesis, genomic instability, and ensuing resistance to current cancer therapy. Additionally, stalled or collapsed DNA replication forks present a unique challenge to the double-strand DNA break (DSB) repair system. Of the various inducible DNA lesions, DSBs are the most lethal and thus desirable in the setting of cancer treatment. In mammalian cells, DSBs are typically repaired by the error prone non-homologous end joining pathway (NHEJ) or the high-fidelity homology directed repair (HDR) pathway. Targeting DSB repair pathways using small molecular inhibitors offers a promising mechanism to synergize DNA-damaging drugs and IR while selective inhibition of the NHEJ pathway can induce synthetic lethality in HDR-deficient cancer subtypes. Selective inhibitors of the NHEJ pathway and alternative DSB-repair pathways may also see future use in precision genome editing to direct repair of resulting DSBs created by the HDR pathway. In this review, we highlight the recent advances in the development of inhibitors of the non-phosphatidylinositol 3-kinase-related kinases (non-PIKKs) members of the NHEJ, HDR and minor backup SSA and alt-NHEJ DSB-repair pathways. The inhibitors described within this review target the non-PIKKs mediators of DSB repair including Ku70/80, Artemis, DNA Ligase IV, XRCC4, MRN complex, RPA, RAD51, RAD52, ERCC1-XPF, helicases, and DNA polymerase θ. While the DDR PIKKs remain intensely pursued as therapeutic targets, small molecule inhibition of non-PIKKs represents an emerging opportunity in drug discovery that offers considerable potential to impact cancer treatment.