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Waldenström Macroglobulinemia/Lymphoplasmacytic Lymphoma, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology

Shaji K. Kumar, Natalie S. Callander, Kehinde Adekola, Larry D. Anderson Jr, Muhamed Baljevic, Rachid Baz, Erica Campagnaro, Jorge J. Castillo, Caitlin Costello, Christopher D’Angelo, Benjamin Derman, Srinivas Devarakonda, Noura Elsedawy, Alfred Garfall, Kelly Godby, Jens Hillengass, Leona Holmberg, Myo Htut, Carol Ann Huff, Malin Hultcrantz, Yubin Kang, Sarah Larson, Hans Lee, Michaela Liedtke, Thomas Martin, James Omel, Timothy Robinson, Aaron Rosenberg, Douglas Sborov, Mark A. Schroeder, Daniel Sherbenou, Attaya Suvannasankha, Jason Valent, Asya Nina Varshavsky-Yanovsky, Jenna Snedeker, and Rashmi Kumar

The treatment of Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) has evolved to include several new options. The NCCN Guidelines for WM/LPL provide a framework on which to base decisions regarding diagnosis, treatment, assessment of response to treatment, and follow-up of both newly diagnosed and previously treated WM/LPL.

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Mode of Detection of Second Breast Cancers in Patients Undergoing Surveillance After Treatment of Ductal Carcinoma in Situ

Bethany T. Waites, Liisa Lyon, Gillian Kuehner, Patience Odele, Laurel A. Habel, and Raymond Liu

Background: For patients undergoing posttreatment surveillance after ductal carcinoma in situ (DCIS), the NCCN Guidelines for Breast Cancer recommend annual breast imaging and physical examination every 6 to 12 months for 5 years, and then annually. The aim of our study was to evaluate the modes of detection (imaging, patient reported, or physical examination) of second cancers in a cohort of patients undergoing surveillance after primary DCIS treatment to better inform surveillance recommendations. Methods: We performed a retrospective cohort study of patients with DCIS treated between January 1, 2008, and December 31, 2011, within a large integrated health care system. Information on patient demographics, index DCIS treatment, tumor characteristics, and mode of detection of second breast cancer was obtained from the electronic health record or chart review. Results: Our study cohort consisted of 1,550 women, with a median age of 59 years at diagnosis. Surgical treatment of DCIS included lumpectomy (75.0%; n=1,162), unilateral mastectomy (21.1%; n=327), or bilateral mastectomy (3.9%; n=61), with or without sentinel lymph node biopsy. Additionally, 44.4% (n=688) and 28.3% (n=438) received radiation and endocrine therapies, respectively. Median follow-up was 10 years, during which 179 (11.5%) women were diagnosed with a second breast cancer. Of the second cancers, 43.0% (n=77) were ipsilateral and 54.8% (n=98) contralateral, and 2.2% (n=4) presented with distant metastases; 61.5% (n=110) were invasive, 36.3% (n=65) were DCIS, and 2.2% (n=4) were Paget’s disease. Second breast cancers were imaging-detected in 74.3% (n=133) of cases, patient-detected in 20.1% (n=36), physician-detected in 2.2% (n=4), and detected incidentally on imaging or pathology from procedures unrelated to oncologic care in 3.4% (n=6). Conclusions: In our cohort of patients undergoing surveillance following diagnosis and treatment of DCIS, 2% of second breast cancers were detected by a clinical breast examination. This suggests that survivorship care should prioritize mammography and patient education regarding breast self-examination and symptoms that warrant evaluation to detect second breast cancers.

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Associations Between Patient Experience With Care, Race and Ethnicity, and Receipt of CRC Treatment Among SEER-CAHPS Patients With Multiple Comorbidities

Stephanie Navarro, Jennifer Tsui, Afsaneh Barzi, Mariana C. Stern, Trevor Pickering, and Albert J. Farias

Background: Patients with colorectal cancer (CRC) and multiple comorbidities are less likely to receive guideline-concordant treatment (GCT), a disparity exacerbated by racial and ethnic disparities in GCT. Yet, positive patient experiences with care are associated with more appropriate care use. We investigated associations between patient experiences with care, race and ethnicity, and receipt of GCT for CRC among older adults with multiple comorbidities. Methods: We used SEER-Consumer Assessment of Healthcare Providers and Systems (CAHPS) data to identify participants diagnosed with CRC from 2001 to 2017 at age ≥67 years with additional chronic conditions. Stage-specific GCT was identified following recommendations in the NCCN Guidelines for Colon and Rectal Cancer. Patient experiences with care were identified from CAHPS surveys. Multivariable log-binomial regression estimated associations between race and ethnicity and receipt of GCT by experiences with care. Results: A total of 2,612 patients were included. Those reporting excellent experience with getting care quickly were 5% more likely to receive GCT than those reporting less-than-excellent experience (relative risk [RR], 1.05; 95% CI, 1.04–1.05). When reporting less-than-excellent experience with getting care quickly, non-Hispanic Black (NHB) patients were less likely than non-Hispanic White (NHW) patients to receive GCT (RR, 0.80; 99.38% CI, 0.78–0.82), yet NHB patients were more likely to receive GCT than NHW patients when reporting excellent experience (RR, 1.05; 99.38% CI, 1.02–1.09). When reporting less-than-excellent experience with getting needed care, Hispanic patients were less likely than NHW patients to receive GCT (RR, 0.91; 99.38% CI, 0.88–0.94), yet Hispanic patients were more likely to receive GCT than NHW patients when reporting excellent experience (RR, 1.06; 99.38% CI, 1.03–1.08). Conclusions: Although excellent patient experience among those with multiple comorbidities may not be strongly associated with receipt of GCT for CRC overall, improvements in experiences of accessing care among NHB and Hispanic patients with CRC and additional comorbidities may aid in mitigating racial and ethnic disparities in receipt of GCT.

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Impact of Recombinant Granulocyte Colony-Stimulating Factor During Neoadjuvant Therapy on Outcomes of Resected Pancreatic Cancer

Pranav Murthy, Mazen S. Zenati, Samer S. AlMasri, Annissa DeSilva, Aatur D. Singhi, Alessandro Paniccia, Kenneth K. Lee, Richard L. Simmons, Nathan Bahary, Michael T. Lotze, and Amer H. Zureikat

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by chronic inflammation and a tolerogenic immune response. The granulocyte colony-stimulating factor (G-CSF)–neutrophil axis promotes oncogenesis and progression of PDAC. Despite frequent use of recombinant G-CSF in the management and prevention of chemotherapy-induced neutropenia, its impact on oncologic outcomes of patients with resected PDAC is unclear. Patients and Methods: This cohort study assessing the impact of G-CSF administration was conducted on 351 patients with PDAC treated with neoadjuvant therapy (NAT) and pancreatic resection at a high-volume tertiary care academic center from 2014 to 2019. Participants were identified from a prospectively maintained database and had a median follow-up of 45.8 months. Results: Patients receiving G-CSF (n=138; 39.3%) were younger (64.0 vs 66.7 years; P=.008), had lower body mass index (26.5 vs 27.9; P=.021), and were more likely to receive 5-FU–based chemotherapy (42.0% vs 28.2%; P<.0001). No differences were observed in baseline or clinical tumor staging. Patients receiving G-CSF were more likely to have an elevated (>5.53) post-NAT neutrophil-to-lymphocyte ratio (45.0% vs 29.6%; P=.004). G-CSF recipients also demonstrated higher circulating levels of neutrophil extracellular traps (+709 vs –619 pg/mL; P=.006). On multivariate analysis, G-CSF treatment was associated with perineural invasion (hazard ratio [HR], 2.65; 95% CI, 1.16–6.03; P=.021) and margin-positive resection (HR, 1.67; 95% CI, 1.01–2.77; P=.046). Patients receiving G-CSF had decreased overall survival (OS) compared with nonrecipients (median OS, 29.2 vs 38.7 months; P=.001). G-CSF administration was a negative independent predictor of OS (HR, 2.02; 95% CI, 1.45–2.79; P<.0001). In the inverse probability weighted analysis of 301 matched patients, neoadjuvant G-CSF administration was associated with reduced OS. Conclusions: In patients with localized PDAC receiving NAT prior to surgical extirpation, G-CSF administration may be associated with worse oncologic outcomes and should be further evaluated.

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Impact of the Identification of Nonhuman Genetic Signatures in the Diagnosis and Management of Carcinoma of Unknown Primary

Arantzazu Barquín García, Sara Palacios-Zambrano, Felipe Lozano Alarcón, Beatriz Paumard-Hernández, Miguel Quiralte Pulido, Paloma Navarro, Laura Rodríguez, Isabel Salas Villar, and Jesús García-Donas

This report presents the case of a 62-year-old woman who was diagnosed in 1999 with stage I cervical carcinoma treated by surgical resection. In 2021, she presented to the emergency department with a complaint of predominantly right-sided lower back pain. A CT scan of the lumbosacral region revealed a bone lesion in the L5 vertebra and retroperitoneal lymphadenopathies suggestive of malignancy. Histology of the L5 vertebra biopsy showed a poorly differentiated carcinoma with an inconclusive immunophenotypic profile. Treatment for carcinoma of unknown primary was started with a combination of carboplatin and paclitaxel every 21 days. A genomic study of the biopsy specimen performed on the FoundationOne CDx platform identified a nonhuman genetic signature compatible with HPV. The presence of HPV 18 DNA in the specimen was confirmed by PCR-reverse dot blot, and the immunophenotypic profile was expanded, revealing strong and diffuse p16 expression, thus corroborating the molecular findings. In view of these findings, the case was reclassified as a recurrence of the cervical adenocarcinoma that had been diagnosed and treated 23 years earlier. Based on the new results, and according to first-line cervical carcinoma protocols, bevacizumab at 15 mg/kg every 21 days was added to her chemotherapy regimen. The identification of HPV DNA sequences by next-generation sequencing facilitated the correct diagnosis and led to a modification of the first-line therapeutic approach.

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Development and Validation of a Nomogram for Predicting Postoperative Early Relapse and Survival in Hepatocellular Carcinoma

Yongzhu He, Laihui Luo, Renfeng Shan, Junlin Qian, Lifeng Cui, Zhao Wu, Shuju Tu, WenJian Zhang, Wei Lin, Hongtao Tang, Zeyu Huang, Zhigang Li, Shengping Mao, Hui Li, Zemin Hu, Liping Liu, Wei Shen, Kun He, and Yong Li

Background: Early relapse after hepatectomy presents a significant challenge in the treatment of hepatocellular carcinoma (HCC). The aim of this study was to construct and validate a novel nomogram model for predicting early relapse and survival after hepatectomy for HCC. Patients and Methods: We conducted a large-scale, multicenter retrospective analysis of 1,505 patients with surgically treated HCC from 4 medical centers. All patients were randomly divided into either the training cohort (n=1,053) or the validation cohort (n=452) in a 7:3 ratio. A machine learning–based nomogram model for prediction of HCC was established by integrating multiple risk factors that influence early relapse and survival, which were identified from preoperative clinical data and postoperative pathologic characteristics of the patients. Results: The median time to early relapse was 7 months, whereas the median time from early relapse to death was only 19 months. The concordance indexes of the postoperative nomogram for predicting disease-free survival and overall survival were 0.741 and 0.739, respectively, with well-calibrated curves demonstrating good consistency between predicted and observed outcomes. Moreover, the accuracy and predictive performance of the postoperative nomograms were significantly superior to those of the preoperative nomogram and the other 7 HCC staging systems. The patients in the intermediate- and high-risk groups of the model had significantly higher probabilities of early and critical recurrence (P<.001), whereas those in the low-risk group had higher probabilities of late and local recurrence (P<.001). Conclusions: This postoperative nomogram model can better predict early recurrence and survival and can serve as a useful tool to guide clinical treatment decisions for patients with HCC.

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Volume 21 (2023): Issue 12 (Dec 2023)

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Effect of Adapted Physical Activity in Patients With Advanced Pancreatic Cancer: The APACaP GERCOR Randomized Trial

Cindy Neuzillet, Olivier Bouché, Christophe Tournigand, Benoist Chibaudel, Lucile Bauguion, Leïla Bengrine-Lefevre, Daniel Lopez-Trabada Ataz, May Mabro, Jean-Philippe Metges, Denis Péré-Vergé, Thierry Conroy, Astrid Lièvre, Morgan Andre, Françoise Desseigne, François Goldwasser, Julie Henriques, Amélie Anota, and Pascal Hammel

Background: The impact of adapted physical activity (APA) on health-related quality of life (HRQoL) in patients with advanced pancreatic ductal adenocarcinoma (aPDAC) is unknown. This study evaluated whether APA in addition to standard care improved HRQoL in patients who have aPDAC who are receiving first-line chemotherapy. Patients and Methods: Patients with locally advanced/metastatic PDAC and an ECOG performance status of 0 to 2 were randomized (1:1) to receive standard care (standard arm) or standard care plus a home-based 16-week APA program (APA arm). The primary objective was the effect of the APA program on 3 dimensions of the EORTC QLQ-C30: global health status, physical function, and fatigue at week 16 (W16), with a one-sided type I error of 0.017 for each dimension. The primary HRQoL analysis was performed in patients with available baseline and W16 scores for the dimensions (ie, the modified intention-to-treat population 1 [mITT1]), and secondary longitudinal HRQoL analyses using the mixed model for repeated measures (MMRM) and time until definitive deterioration (TUDD) methods were performed in the mITT1 population and in patients with baseline and at least one follow-up questionnaire (mITT2 population). A difference of ≥5 points was considered to be clinically relevant. Results: Of 326 included patients, 313 were randomized to the standard (n=157) or APA (n=156) arms. In the mITT1 population (n=172), the mean differences in global health status, physical function, and fatigue at W16 adjusted from baseline were −0.98 (SD, 23.9; P=.39), −2.08 (SD, 21.3; P=.26), and 4.16 (SD, 29.2; P=.17), respectively, showing a non–statistically significant benefit with APA. In the mITT2 population (n=259), APA was associated with statistically significant and clinically relevant improvement in 5 and 8 dimensions of the HRQoL in the longitudinal MMRM and TUDD analyses, respectively. Conclusions: APA improved several dimensions of HRQoL in patients with aPDAC receiving first-line chemotherapy and standard care.

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Highlights of the NCCN Oncology Research Program

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Integrating Immune Therapies for the Treatment of Multiple Myeloma

Lekha Mikkilineni and Surbhi Sidana

Patients with relapsed or refractory multiple myeloma (RRMM) that is refractory to a proteasome inhibitor, an immunomodulatory drug (IMiD), and an anti-CD38 antibody (triple-class refractory MM) have poor outcomes. Recently, 2 classes of T-cell engaging therapies—CAR T-cell therapy and bispecific T-cell engaging antibodies (BsAbs)—have resulted in unprecedented response rates and survival outcomes in these heavily pretreated patients. The most common targets are BCMA and GPRC5D, with other targets in development. The main classes of adverse effects include cytokine release syndrome, neurotoxicity, infections, and cytopenias, as well as adverse effects unique to specific products. As of September 2023, 2 BCMA-targeting CAR-T cell products, 2 BCMA-targeting BsAbs, and 1 GPRC5D-targeting BsAb, are FDA-approved for standard-of-care use in patients with RRMM who received at least 4 prior lines of therapy, including prior treatment with a proteasome inhibitor, an IMiD, and an anti-CD38 antibody. Earlier-line use is under investigation and has shown promising results. Several other investigational CAR-T constructs and bispecific antibodies are in clinical development. As these therapies become more widely used, including in earlier-line setting, efforts to understand optimal sequencing and mitigate toxicities remain critical.