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Mesothelioma: Pleural, Version 1.2024

Featured Updates to the NCCN Guidelines

James Stevenson, David S. Ettinger, Douglas E. Wood, Dara L. Aisner, Wallace Akerley, Jessica R. Bauman, Ankit Bharat, Debora S. Bruno, Joe Y. Chang, Lucian R. Chirieac, Malcolm DeCamp, Aakash Desai, Thomas J. Dilling, Jonathan Dowell, Gregory A. Durm, Marina C. Garassino, Scott Gettinger, Travis E. Grotz, Matthew A. Gubens, Rudy P. Lackner, Michael Lanuti, Jules Lin, Billy W. Loo Jr, Christine M. Lovly, Fabien Maldonado, Erminia Massarelli, Daniel Morgensztern, Trey C. Mullikin, Thomas Ng, Gregory A. Otterson, Dawn Owen, Sandip P. Patel, Tejas Patil, Patricio M. Polanco, Gregory J. Riely, Jonathan Riess, Theresa A. Shapiro, Aditi P. Singh, Alda Tam, Tawee Tanvetyanon, Jane Yanagawa, Stephen C. Yang, Edwin Yau, Kristina Gregory, and Lisa Hang

Mesothelioma is a rare cancer that originates from the mesothelial surfaces of the pleura and other sites, and is estimated to occur in approximately 3,500 people in the United States annually. Pleural mesothelioma is the most common type and represents approximately 85% of these cases. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pleural mesothelioma. These NCCN Guidelines Insights highlight significant updates to the NCCN Guidelines for Mesothelioma: Pleural, including revised guidance on disease classification and systemic therapy options.

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Update on the Sentinel Node Procedure in Vulvar Cancer

Willemijn L. van der Kolk, Joost Bart, Ate J.G. van der Zee, and Maaike H.M. Oonk

Early-stage vulvar cancer is managed by a local excision of the primary tumor and, if indicated, a sentinel node (SN) biopsy to assess the need for further groin treatment. With the SN procedure, many patients can be treated less radically and will experience less complications and morbidity compared with an inguinofemoral lymphadenectomy (IFL). Still, the SN procedure can be further optimized. Different tracers for detecting the SN are being investigated, aiming to optimize detection rates and decrease the burden of the procedure and short-term complications. Until now, no standardized protocols exist for the pathologic workup of the SN, possibly leading to discrepancies in detection of metastases between institutes using different methods. New techniques, such as one-step nucleic amplification, seem to have potential in accurately detecting metastases in other cancers, but have not yet been investigated in vulvar squamous cell carcinoma (VSCC). Furthermore, several studies have investigated the possibility to broaden the indications for the SN procedure, such as its use in recurrent disease, larger tumors, or multifocal tumors. Although these studies show encouraging results, cohorts are small and further studies are needed. Prospective studies are currently investigating these subgroups. Lastly, several studies investigated optimization of groin treatment of patients with a metastatic SN. Inguinofemoral radiotherapy is a good alternative to IFL in patients with micrometastases in the SN, with comparable efficacy and less treatment-related morbidity. Reduction of the radicality of groin treatment is also possible in other ways, such as omitting contralateral IFL in patients with lateralized tumors and a unilateral metastatic SN. In conclusion, the SN procedure is an established procedure in early-stage VSCC, although optimization of the technique, pathologic workup, indications, and treatment in the setting of metastatic disease are the subject of ongoing research.

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Vulvar Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology

Nadeem R. Abu-Rustum, Catheryn M. Yashar, Rebecca Arend, Emma Barber, Kristin Bradley, Rebecca Brooks, Susana M. Campos, Junzo Chino, Hye Sook Chon, Marta Ann Crispens, Shari Damast, Christine M. Fisher, Peter Frederick, David K. Gaffney, Stephanie Gaillard, Robert Giuntoli II, Scott Glaser, Jordan Holmes, Brooke E. Howitt, Kari Kendra, Jayanthi Lea, Nita Lee, Gina Mantia-Smaldone, Andrea Mariani, David Mutch, Christa Nagel, Larissa Nekhlyudov, Mirna Podoll, Kerry Rodabaugh, Ritu Salani, John Schorge, Jean Siedel, Rachel Sisodia, Pamela Soliman, Stefanie Ueda, Renata Urban, Stephanie L. Wethington, Emily Wyse, Kristine Zanotti, Nicole McMillian, and Sara Espinosa

Vulvar cancer is annually diagnosed in an estimated 6,470 individuals and the vast majority are histologically squamous cell carcinomas. Vulvar cancer accounts for 5% to 8% of gynecologic malignancies. Known risk factors for vulvar cancer include increasing age, infection with human papillomavirus, cigarette smoking, inflammatory conditions affecting the vulva, and immunodeficiency. Most vulvar neoplasias are diagnosed at early stages. Rarer histologies exist and include melanoma, extramammary Paget’s disease, Bartholin gland adenocarcinoma, verrucous carcinoma, basal cell carcinoma, and sarcoma. This manuscript discusses recommendations outlined in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for treatments, surveillance, systemic therapy options, and gynecologic survivorship.

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Oncologist Perceptions of Racial Disparity, Racial Anxiety, and Unconscious Bias in Clinical Interactions, Treatment, and Outcomes

Alexandrina Balanean, Emily Bland, Ajeet Gajra, Yolaine Jeune-Smith, Andrew J. Klink, Harlen Hays, and Bruce A. Feinberg

Background: Cancer spares no demographic or socioeconomic group; it is indeed the great equalizer. But its distribution is not equal; when structural discrimination concentrates poverty and race, zip code surpasses genetic code in predicting outcomes. Compared with White patients in the United States, Black patients are less likely to receive appropriate treatment and referral to clinical trials, genetic testing, or palliative care/hospice. Methods: In 2021, we administered a survey to 369 oncologists measuring differences in perceptions surrounding racial disparity, racial anxiety, and unconscious bias and adverse influence on clinical interactions, treatment, and outcomes for non-White patients. We analyzed responses by generational age group, sex/gender, race/ethnicity, US region, and selection of “decline to respond.” Results: The most significant differences occurred by age group followed by race/ethnicity. Racial disparity was perceived as moderate to very high by 84% of millennial, 69% of Generation X, and 57% of baby boomer oncologists, who were also 86% more likely than millennials and 63% more likely than Generation Xers to perceive low/nonexistent levels of racial anxiety/unconscious bias. Conclusions: Most oncologists rarely or never perceived racial anxiety/unconscious bias as adversely influencing clinical treatment or survival outcomes in non-White patients, and White oncologists were 85% more likely than non-White oncologists to perceive rare/nonexistent influence on referral of non-White patients to palliative care/hospice. The discrepancy between 62% of oncologists perceiving moderate to very high levels of racial anxiety/unconscious bias and 37% associating them with adverse influence on non-White patients shows a disconnect, especially among older oncologists (baby boomers), who were also least likely to select the decline option. Together, these factors hinder effective patient–provider communication and result in differential care and outcomes. Oncologists should uncover their own perceptions surrounding racial disparity, racial anxiety, and unconscious bias and modify their behaviors accordingly. It is this simple—and this complicated. Cancer does not discriminate, and neither should cancer care.

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Pilot Randomized Controlled Trial of an Educational Video for CAR T-Cell Therapy Recipients

P. Connor Johnson, Tejaswini Dhawale, Richard A. Newcomb, Ana Barata, Kyle Karpinski, Mitchell W. Lavoie, Dagny Vaughn, Kathleen Hennessey, David Schneider, Hermioni L. Amonoo, Angelo Volandes, and Areej El-Jawahri

Background: CAR T-cell therapy has transformed the treatment of hematologic malignancies, but it is complex and challenging to convey to patients. Educational video interventions are efficacious for improving patient knowledge about cancer therapeutics and informing their care preferences, yet no educational videos have been evaluated in CAR T-cell therapy. Methods: We conducted a randomized controlled trial comparing an educational video versus usual care in adults (age ≥18 years) with hematologic malignancies receiving CAR T-cell therapy at Massachusetts General Hospital. Intervention participants watched a 13-minute video depicting how CAR T-cell therapy works, logistics, toxicities, prognosis, recovery, and approaches for dealing with prognostic uncertainty. The primary outcome was feasibility (≥60% enrollment rate). Secondary outcomes included acceptability (≥80% reporting comfort with the video), patients’ knowledge about CAR T-cell therapy (10-item test), and self-efficacy (Communication and Attitudinal Self-Efficacy Scale–Cancer), decision satisfaction (Decision Conflict Scale), psychological distress (Hospital Anxiety and Depression Scale), and preference for CAR T-cell therapy. Results: We enrolled 79% (80/101) of eligible patients. Of that group, 91% (30/33) reported being very or somewhat comfortable watching the video, and 94% (31/33) would definitely or probably recommend the video. At 1 month, participants in the video arm reported higher self-efficacy (mean difference [MD], 9.2 [95% CI, –4.0 to 22.3]; Cohen’s d, 0.32), decision satisfaction (MD, 2.5 [95% CI, 0.7–4.2]; Cohen’s d, 0.67), and lower anxiety (MD, –0.8 [95% CI, –2.5 to 0.7]; Cohen’s d, 0.26) compared with participants in the usual care arm. At 1 week, both arms reported high preferences for CAR T-cell therapy (video arm, 94% [33/35]; usual care, 84% [27/32]). Conclusions: We found that an educational video for patients receiving CAR T-cell therapy was feasible and acceptable. The educational video demonstrated promising preliminary effects on patient self-efficacy and decision satisfaction and warrants further study.

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Outcomes of a Dietary Intervention to Reduce Bladder Cancer Recurrence and Progression in Survivors of Non–Muscle-Invasive Bladder Cancer

Karen H. Kim Yeary, Han Yu, Margaret Gates Kuliszewski, Qiang Li, Susan E. McCann, Rachel Pratt, Frances G. Saad-Harfouche, Zinian Wang, Nikia Clark, Chong Wang, Elizabeth DiCarlo, and Li Tang

Background: As one of the 10 most common cancers in the United States, bladder cancer is the most expensive cancer to treat. Most bladder cancers (70%–80%) are diagnosed at early stages as non–muscle-invasive bladder cancer (NMIBC), which can be removed. However, 50% to 80% of NMIBC recurs within 5 years, and 15% to 30% progresses with poor survival. Besides life-long surveillance, current treatment is limited. Preclinical and epidemiologic evidence suggest that dietary isothiocyanates (ITCs) in cruciferous vegetables (Cruciferae) could be a noninvasive and cost-effective strategy to improve NMIBC prognosis. Yet, a Cruciferae intervention that increases ITC exposure in NMIBC survivors has not been tested. Thus, the primary aim of this study was to test the effect of a Cruciferae intervention on urinary ITC levels and Cruciferae intake in NMIBC survivors. Patients and Methods: We conducted a 2-arm, double-blinded, randomized controlled trial to test the efficacy of a Cruciferae intervention against a general fruit and vegetable intervention (control) for NMIBC survivors. Both 6-month interventions consisted of mailed educational materials, a live call with staff to review the materials, and 11 interactive voice response calls. We anticipated that our Cruciferae intervention (Power to Redefine Your Health [POW-R Health]) would increase Cruciferae intake to 1 cup/day (secondary outcome), thus raising urinary ITC levels to 10 µM (primary outcome) from baseline to 6-month follow-up. Results: We randomized 49 patients with NMIBC diagnosed in 2018 through 2019, and retained 42 patients at 6-month follow-up. The treatment group reported 0.94 cups (95% CI, 0.24–1.65; P=.010) higher Cruciferae intake (treatment, 1.37 ± 1.19 cups vs control, 0.56 ± 0.72 cups) and increased urinary ITC levels by 11.1 μmol/g creatinine (treatment, 26.2 ± 20.9 vs control, 7.8 ± 11.5; P=.027) at 6-month follow-up compared with the control group. Conclusions: Our dietary intervention is the first to significantly increase Cruciferae intake and urinary ITC levels in NMIBC survivors, demonstrating an increase in ITC to levels that significantly decrease risk of disease-specific survival. A future randomized controlled trial testing POW-R Health on bladder cancer recurrence and progression is warranted. If proven to improve bladder cancer outcomes, our intervention has the potential to be a noninvasive, cost-effective, easily accessible way for NBMIC survivors to improve their bladder cancer prognosis.

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Risk Factors Associated With Distress Among Postoperative Patients in an Academic Gynecologic Oncology Practice

Maya E. Gross, Janelle N. Sobecki, Chan Park, Menggang Yu, and Sumer K. Wallace

Background: Distress among gynecologic oncology patients correlates with poor clinical outcomes and decreased quality of life. The purpose of this study was to determine risk factors for elevated NCCN Distress Thermometer (DT) results among postoperative gynecologic oncology patients. Patients and Methods: We performed a retrospective chart review of all postoperative visits over a 5-year period. NCCN DT results were analyzed as both discretized values (DT ≤3 = low distress; DT 4–8 = moderate distress; DT ≥9 = high distress) and continuous variables. Patients with a DT score ≥4 were referred to social work. Univariate and multivariate regression analyses were performed to compare NCCN DT results with clinical and sociodemographic variables. Statistical significance was P<.05. Results: In total, 1,795 NCCN DT results were included, with uterine (37.72%) being the most common disease site. Benign pathology was known prior to completion of the NCCN DT in 13.15% of patients. Most patients (71.75%) endorsed low levels of distress. Moderate/High levels of distress were reported by 28.25% of patients. Increasing levels of distress were significantly associated with younger age (P=.006), history of depression (P≤.001), status as a current smoker (P=.028), and history of asthma (P=.041). Knowledge of benign pathology was associated with low levels of distress (P=.002). Procedure type and disease site were not associated with distress. Conclusions: More than one-fourth of postoperative patients in a gynecologic oncology practice reported moderate or high distress. Distress was highest among those with malignancy regardless of disease site or surgical intervention. Benign pathology correlated with decreased distress. Identified associations with distress provide opportunities for prevention, early intervention, and tailored counseling.

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Impact of Pain on Symptom Burden in Chemotherapy-Induced Peripheral Neurotoxicity

Fawaz Mayez Mahfouz, Tiffany Li, Hannah C. Timmins, Lisa G. Horvath, Michelle Harrison, Peter Grimison, Gavin Marx, David Goldstein, and Susanna B. Park

Background: Chemotherapy-induced peripheral neurotoxicity (CIPN) affects the quality of life of cancer survivors. However, the impact of pain on symptom burden remains undefined. This study aimed to define differences in the clinical symptom profile of patients with painful and nonpainful CIPN. Patients and Methods: A total of 579 participants (median age, 59 years [IQR, 19 years]; F=66%) were assessed cross-sectionally 6 months posttreatment. CIPN severity was graded using multiple methods, including patient-reported outcome measures, a clinically graded scale (NCI-CTCAE), and a neurologic examination score. Participants were classified into subgroups based on patient symptom report, with painful CIPN characterized by the presence of shooting/burning pain, and nonpainful CIPN characterized by the presence of numbness or tingling without shooting/burning pain. Behavioral changes were assessed via structured patient interview regarding symptom impact on sleep, exercise, and treatment-seeking. Results: Among 579 participants, 24% (n=140) reported painful CIPN, 48% (n=280) reported nonpainful CIPN, and 28% (n=159) had no CIPN. Participants with painful CIPN demonstrated higher CIPN severity than those with nonpainful CIPN across multiple measures, including NCI-CTCAE, neurologic grading, and patient report (all P<.05). Participants with painful CIPN were more likely to report that their symptoms affected their ability to exercise (P=.007), produced sleep impairment, and increased treatment-seeking behavior due to their symptoms (both P<.001) compared with participants with nonpainful CIPN. Conclusions: Overall, participants with painful CIPN reported higher scores across all CIPN severity measures, including behavioral changes. This study underlines the need for accurate identification of different CIPN subgroups in hopes of informing better treatment and rehabilitation options for cancer survivors with painful CIPN.

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Response of a Novel KANK1::ALK Fusion to Alectinib in an Advanced Lung Adenocarcinoma: A Case Report

Quanying Tang, Tong Li, Fan Ren, Xuanguang Li, WeiBo Cao, Haochuan Yu, Fuling Mao, Cancan Cao, Lingling Zu, and Song Xu

More than 90 distinct fusion partners of ALK rearrangement have been identified. Different ALK fusions may exhibit different sensitivities to ALK tyrosine kinase inhibitors. The emergence of rare fusions poses significant challenges to targeted therapies. This study aimed to investigate the response of KANK1::ALK fusion to alectinib in an advanced lung adenocarcinoma. A novel KANK1::ALK fusion was identified by next-generation sequencing (NGS) and Ventana immunohistochemistry assessments. A 73-year-old woman who had never smoked was admitted with hemoptysis in May 2020. PET/CT revealed a nodule in the left upper lobe, with bilateral pulmonary and multiple lymph node metastases. The upper lobe nodule of the left lung was diagnosed as adenocarcinoma through bronchofiberscopy biopsy, resulting in a clinical diagnosis of stage IVA (cT1c,N3,M1a). Because the biopsy tissue was insufficient for NGS analysis, a blood-based genetic analysis was performed, revealing the presence of KRAS p.Q61R mutations. The patient received carboplatin and pemetrexed with pembrolizumab as first-line therapy, followed by maintenance therapy of pembrolizumab monotherapy. Although the tumor initially showed significant shrinkage, it unfortunately progressed further after 11 months. Subsequently, the patient was given carboplatin and pemetrexed with pembrolizumab again, but the tumor progression continued. An NGS using a rebiopsy of the left upper lobe tumor suggested a KANK1::ALK fusion. Alectinib was prescribed in January 2022, and a durable partial response was observed after 18 months. ALK rearrangements were observed in the broader spectrum of lung cancers. This study provided a potential treatment option for patients with KANK1::ALK fusions. Further studies are needed to understand the function of these fusions.