Patricia I. Moreno, Frank J. Penedo, Felicia M. Knaul, Carina Oltmann, Michael T. Huber, and Mariana Khawand-Azoulai
Saurabh Zanwar, Morie A. Gertz, and Eli Muchtar
Immunoglobulin light chain (AL) amyloidosis is a clonal plasma cell disorder with multiple clinical presentations. The diagnosis of AL amyloidosis requires a high index of suspicion, making a delay in diagnosis common, which contributes to the high early mortality seen in this disease. Establishing the diagnosis of AL amyloidosis requires the demonstration of tissue deposition of amyloid fibrils. A bone marrow biopsy and fat pad aspirate performed concurrently have a high sensitivity for the diagnosis of AL amyloidosis and negate the need for organ biopsies in most patients. An accurate diagnosis requires amyloid typing via additional testing, including tissue mass spectrometry. Prognostication for AL amyloidosis is largely driven by the organs impacted. Cardiac involvement represents the single most important prognostic marker, and the existing staging systems are driven by cardiac biomarkers. Apart from organ involvement, plasma cell percentage on the bone marrow biopsy, specific fluorescence in situ hybridization findings, age at diagnosis, and performance status are important prognostic markers. This review elaborates on the diagnostic testing and prognostication for patients with newly diagnosed AL amyloidosis.
Matteo Lambertini, Marcello Ceppi, Richard A. Anderson, David A. Cameron, Marco Bruzzone, Maria Alice Franzoi, Claudia Massarotti, Sarra El-Abed, Yingbo Wang, Christophe Lecocq, Paolo Nuciforo, Rebecca Rolyance, Lajos Pusztai, Joohyuk Sohn, Maria Maddalena Latocca, Luca Arecco, Barbara Pistilli, Kathryn J. Ruddy, Alberto Ballestrero, Lucia Del Mastro, Fedro A. Peccatori, Ann H. Partridge, Cristina Saura, Michael Untch, Martine Piccart, Serena Di Cosimo, Evandro de Azambuja, and Isabelle Demeestere
Background: The potential gonadotoxicity of anti-HER2 agents remains largely unknown, and limited, conflicting evidence exists for taxanes. Antimüllerian hormone (AMH) is an established biomarker of ovarian reserve that may aid in quantifying anticancer treatment–induced gonadotoxicity. Patients and Methods: The present biomarker analysis of the randomized phase III neoadjuvant NeoALTTO trial included premenopausal women aged ≤45 years at diagnosis of HER2-positive early breast cancer with available frozen serum samples at baseline (ie, before anticancer treatments), at week 2 (ie, the “biological window” of anti-HER2 therapy alone), and/or at the time of surgery (ie, after completing paclitaxel + anti-HER2 therapy, before starting adjuvant chemotherapy). Results: The present analysis included 130 patients with a median age of 38 years (interquartile ratio [IQR], age 33–42 years). AMH values at the 3 time points differed significantly (P<.001). At baseline, median AMH levels were 1.29 ng/mL (IQR, 0.56–2.62 ng/mL). At week 2, a small but significant reduction in AMH levels was observed (median, 1.10 ng/mL; IQR, 0.45–2.09 ng/mL; P<.001). At surgery, a larger significant decline in AMH levels was observed (median, 0.01 ng/mL; IQR, 0.01–0.03 ng/mL; P<.001). Although the type of anti-HER2 treatment (trastuzumab and/or lapatinib) did not seem to impact the results, age and pretreatment ovarian reserve had a major influence on treatment-induced gonadotoxicity risk. Conclusions: This NeoALTTO biomarker analysis showed that anti-HER2 therapies alone had limited gonadotoxicity but that the addition of weekly paclitaxel resulted in marked AMH decline with possible negative implications for subsequent ovarian function and fertility.
Sanjay Chawla, Cristina Gutierrez, Prabalini Rajendram, Kenneth Seier, Kay See Tan, Kara Stoudt, Marian Von-Maszewski, Jorge L. Morales-Estrella, Natalie T. Kostelecky, and Louis P. Voigt
Background: Patients with cancer who require cardiopulmonary resuscitation (CPR) historically have had low survival to hospital discharge; however, overall CPR outcomes and cancer survival have improved. Identifying patients with cancer who are unlikely to survive CPR could guide and improve end-of-life discussions prior to cardiac arrest. Methods: Demographics, clinical variables, and outcomes including immediate and hospital survival for patients with cancer aged ≥18 years who required in-hospital CPR from 2012 to 2015 were collected. Indicators capturing the overall declining clinical and oncologic trajectory (ie, no further therapeutic options for cancer, recommendation for hospice, or recommendation for do not resuscitate) prior to CPR were determined a priori and manually identified. Results: Of 854 patients with cancer who underwent CPR, the median age was 63 years and 43.6% were female; solid cancers accounted for 60.6% of diagnoses. A recursive partitioning model selected having any indicator of declining trajectory as the most predictive factor in hospital outcome. Of our study group, 249 (29%) patients were found to have at least one indicator identified prior to CPR and only 5 survived to discharge. Patients with an indicator were more likely to die in the hospital and none were alive at 6 months after discharge. These patients were younger (median age, 59 vs 64 years; P≤.001), had a higher incidence of metastatic disease (83.0% vs 62.9%; P<.001), and were more likely to undergo CPR in the ICU (55.8% vs 36.5%; P<.001) compared with those without an indicator. Of patients without an indicator, 145 (25%) were discharged alive and half received some form of cancer intervention after CPR. Conclusions: Providers can use easily identifiable indicators to ascertain which patients with cancer are at risk for death despite CPR and are unlikely to survive to discharge. These findings can guide discussions regarding utility of resuscitation and the lack of further cancer interventions even if CPR is successful.
Giovanni Palladini and Paolo Milani
Systemic light chain (AL) amyloidosis is caused by a B-cell (most commonly plasma cell) clone that produces a toxic light chain that forms amyloid fibrils in tissues and causes severe, progressive organ dysfunction. The clinical presentation is protean, and patients are usually extremely frail, thus requiring careful adaptation of the treatment approach. However, the severity of organ involvement can be accurately assessed with biomarkers that allow a sharp prognostic stratification and precise tailoring of the treatment strategy. Moreover, the availability of biomarker-based response criteria also allows adjustment of the treatment approach over time. The recent completion of 3 large randomized clinical trials has offered new evidence for designing appropriate treatments. All this information has recently been integrated in the joint guidelines of the International Society of Amyloidosis and the European Hematology Association for the treatment of AL amyloidosis. Other clinical trials are underway testing new agents directed against the amyloid clone and the amyloid deposits. Our understanding of the peculiarities of the amyloid clone, as well as our ability to detect residual clonal disease and improve organ dysfunction, are also being refined and will result in more precise personalization of the treatment approach.
NCCN Guidelines® Insights: Central Nervous System Cancers, Version 2.2022
Featured Updates to the NCCN Guidelines
Craig Horbinski, Louis Burt Nabors, Jana Portnow, Joachim Baehring, Ankush Bhatia, Orin Bloch, Steven Brem, Nicholas Butowski, Donald M. Cannon, Samuel Chao, Milan G. Chheda, Andrew J. Fabiano, Peter Forsyth, Pierre Gigilio, Jona Hattangadi-Gluth, Matthias Holdhoff, Larry Junck, Thomas Kaley, Ryan Merrell, Maciej M. Mrugala, Seema Nagpal, Lucien A. Nedzi, Kathryn Nevel, Phioanh L. Nghiemphu, Ian Parney, Toral R. Patel, Katherine Peters, Vinay K. Puduvalli, Jason Rockhill, Chad Rusthoven, Nicole Shonka, Lode J. Swinnen, Stephanie Weiss, Patrick Yung Wen, Nicole E. Willmarth, Mary Anne Bergman, and Susan Darlow
The NCCN Guidelines for Central Nervous System (CNS) Cancers focus on management of the following adult CNS cancers: glioma (WHO grade 1, WHO grade 2–3 oligodendroglioma [1p19q codeleted, IDH-mutant], WHO grade 2–4 IDH-mutant astrocytoma, WHO grade 4 glioblastoma), intracranial and spinal ependymomas, medulloblastoma, limited and extensive brain metastases, leptomeningeal metastases, non–AIDS-related primary CNS lymphomas, metastatic spine tumors, meningiomas, and primary spinal cord tumors. The information contained in the algorithms and principles of management sections in the NCCN Guidelines for CNS Cancers are designed to help clinicians navigate through the complex management of patients with CNS tumors. Several important principles guide surgical management and treatment with radiotherapy and systemic therapy for adults with brain tumors. The NCCN CNS Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding molecular profiling of gliomas.
Bin-Yi Xiao, Xuan Zhang, Tai-Yuan Cao, Dan-Dan Li, Wu Jiang, Ling-Heng Kong, Jing-Hua Tang, Kai Han, Chen-Zhi Zhang, Wei-Jian Mei, Jian Xiao, Zhi-Zhong Pan, Yun-Feng Li, Xiao-Shi Zhang, and Pei-Rong Ding
Background: Our study aimed to evaluate the efficacy and feasibility of neoadjuvant anti–PD-1 treatment for localized mismatch repair–deficient (dMMR) colorectal cancer (CRC). Patients and Methods: The study cohort included patients with localized dMMR CRC who received PD-1 inhibitors as neoadjuvant therapy from 3 medical centers in Southern China. Main eligibility criteria included age between 18 and 75 years, ECOG performance status of 0 or 1, and receipt of ≥2 doses of PD-1 inhibitors. Results: A total of 73 patients were included. Most of the tumors were locally advanced, including 19 (26.0%) T4a and 29 (39.7%) T4b. Most patients (79.5%) received PD-1 inhibitor monotherapy. Objective response per radiologic assessment was achieved in 62 (84.9%) patients, including 17 (23.3%) with complete response (CR) and 45 (61.6%) with partial response, with a median time to response of 9.6 weeks. Patients with T4a/4b disease had a similar response rate as those with T2–3 disease (84.0% vs 85.4%; P=.999). As of writing, a total of 50 patients have undergone surgery. Pathologic CR was achieved in most (57.1%) patients and remained high (59.5%) even among the 38 patients with T4a/4b disease. The 17 patients with CR did not undergo surgery and adopted a watch-and-wait strategy. After a median follow-up of 17.2 months (range, 3.4–45.1 months), the overall median recurrence-free and overall survivals were not reached. Among patients undergoing surgery or achieving CR, the 2-year tumor-specific disease-free and overall survival rates were both 100%. During neoadjuvant treatment, grade 3–4 adverse events occurred in 8 patients; 4 required acute intervention. Severe postoperative complications were recorded in 4 patients, 3 of whom required a second surgery. Conclusions: Neoadjuvant therapy with PD-1 blockade is highly effective for localized dMMR CRC, with an acceptable safety profile and low recurrence rate. This treatment holds promise for becoming the new standard of care for localized dMMR CRCs.