BACKGROUND\nAlthough many patients with intermediate-grade or high-grade (aggressive) non-Hodgkin's lymphoma are cured by combination chemotherapy, the remainder are not cured and ultimately die of their disease. The Ann Arbor classification, used to determine the stage of this disease, does not consistently distinguish between patients with different long-term prognoses. This project was undertaken to develop a model for predicting outcome in patients with aggressive non-Hodgkin's lymphoma on the basis of the patients' clinical characteristics before treatment.\n\n\nMETHODS\nAdults with aggressive non-Hodgkin's lymphoma from 16 institutions and cooperative groups in the United States, Europe, and Canada who were treated between 1982 and 1987 with combination-chemotherapy regimens containing doxorubicin were evaluated for clinical features predictive of overall survival and relapse-free survival. Features that remained independently significant in step-down regression analyses of survival were incorporated into models that identified groups of patients of all ages and groups of patients no more than 60 years old with different risks of death.\n\n\nRESULTS\nIn 2031 patients of all ages, our model, based on age, tumor stage, serum lactate dehydrogenase concentration, performance status, and number of extranodal disease sites, identified four risk groups with predicted five-year survival rates of 73 percent, 51 percent, 43 percent, and 26 percent. In 1274 patients 60 or younger, an age-adjusted model based on tumor stage, lactate dehydrogenase level, and performance status identified four risk groups with predicted five-year survival rates of 83 percent, 69 percent, 46 percent, and 32 percent. In both models, the increased risk of death was due to both a lower rate of complete responses and a higher rate of relapse from complete response. These two indexes, called the international index and the age-adjusted international index, were significantly more accurate than the Ann Arbor classification in predicting long-term survival.\n\n\nCONCLUSIONS\nThe international index and the age-adjusted international index should be used in the design of future therapeutic trials in patients with aggressive non-Hodgkin's lymphoma and in the selection of appropriate therapeutic approaches for individual patients.

A predictive model for aggressive non-Hodgkin's lymphoma

Standardized guidelines for response assessment are needed to ensure comparability among clinical trials in non-Hodgkin's lymphomas (NHL). To achieve this, two meetings were convened among United States and international lymphoma experts representing medical hematology/oncology, radiology, radiation oncology, and pathology to review currently used response definitions and to develop a uniform set of criteria for assessing response in clinical trials. The criteria that were developed include anatomic definitions of response, with normal lymph node size after treatment of 1.5 cm in the longest transverse diameter by computer-assisted tomography scan. A designation of complete response/unconfirmed was adopted to include patients with a greater than 75% reduction in tumor size after therapy but with a residual mass, to include patients-especially those with large-cell NHL-who may not have residual disease. Single-photon emission computed tomography gallium scans are encouraged as a valuable adjunct to assessment of patients with large-cell NHL, but such scans require appropriate expertise. Flow cytometric, cytogenetic, and molecular studies are not currently included in response definitions. Response rates may be the most important objective in phase II trials where the activity of a new agent is important and may provide support for approval by regulatory agencies. However, the goals of most phase III trials are to identify therapies that will prolong the progression-free survival, if not the overall survival, of the treated patients. We hope that these guidelines will serve to improve communication among investigators and comparability among clinical trials until clinically relevant laboratory and imaging studies are identified and become more widely available.

Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas

The purpose of this article is to review the status and limitations of anatomic tumor response metrics including the World Health Organization (WHO) criteria, the Response Evaluation Criteria in Solid Tumors (RECIST), and RECIST 1.1. This article also reviews qualitative and quantitative approaches to metabolic tumor response assessment with 18 F-FDG PET and proposes a draft framework for PET Response Criteria in Solid Tumors (PERCIST), version 1.0. Methods: PubMed searches, including searches for the terms RECIST, positron, WHO, FDG, cancer (including specific types), treatment response, region of interest, and derivative references, were performed. Abstracts and articles judged most relevant to the goals of this report were reviewed with emphasis on limitations and strengths of the anatomic and PET approaches to treatment response assessment. On the basis of these data and the authors’ experience, draft criteria were formulated for PET tumor response to treatment. Results: Approximately 3,000 potentially relevant references were screened. Anatomic imaging alone using standard WHO, RECIST, and RECIST 1.1 criteria is widely applied but still has

https://jnm.snmjournals.org/content/jnumed/50/Suppl_1/122S.full.pdf

From RECIST to PERCIST: Evolving Considerations for PET Response Criteria in Solid Tumors

We describe the use of cubic splines in regression models to represent the relationship between the response variable and a vector of covariates. This simple method can help prevent the problems that result from inappropriate linearity assumptions. We compare restricted cubic spline regression to non-parametric procedures for characterizing the relationship between age and survival in the Stanford Heart Transplant data. We also provide an illustrative example in cancer therapeutics.

Flexible regression models with cubic splines

Background CHOP is a first-generation, combination-chemotherapy regimen consisting of cyclophosphamide, doxorubicin, vincristine, and prednisone that has cured approximately 30 percent of patients with advanced stages of intermediate-grade or high-grade non-Hodgkin's lymphoma in national cooperative-group trials. However, studies at single institutions have suggested that 55 to 65 percent of such patients might be cured by third-generation regimens such as ones consisting of low-dose methotrexate with leucovorin rescue, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD); prednisone, doxorubicin, cyclophosphamide, and etoposide, followed by cytarabine, bleomycin, vincristine, and methotrexate with leucovorin rescue (ProMACE-CytaBOM); and methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B). Methods To make a valid comparison of these regimens, the Southwest Oncology Group and the Eastern Cooperative Oncology Gro...

https://www.nejm.org/doi/pdf/10.1056/NEJM199304083281404

Comparison of a Standard Regimen (CHOP) with Three Intensive Chemotherapy Regimens for Advanced Non-Hodgkin's Lymphoma

Poster: "ECR 2018 / C-1490 / Exploring the added clinical value of breast MRI after contrast-enhanced spectral mammography in patients with invasive lobular carcinoma " by: " T. van Nijnatten 1, M. S. Jochelson2, K. Pinker-Domenig2, D. M. Keating2, J. S. Sung2, M. Morrow2, J. E. Wildberger1, M. Smidt1, M. Lobbes1; 1Maastricht/NL, 2New York, NY/US"

Exploring the added clinical value of breast MRI after contrast-enhanced spectral mammography in patients with invasive lobular carcinoma

Preoperative Immune Checkpoint Inhibition and Cryoablation in Early-Stage Breast Cancer

Reply to "Factors That May Influence Contrast-Enhanced Digital Mammography Findings".

Editorial: CONTRAST MAMMOGRAPHY-A PROMISING TOOL FOR THE PRE-OPERATIVE EVALUATION OF LOBULAR BREAST CANCER


 Background: The Lobular Breast Cancer Alliance (LBCA) is an advocacy organization guided by an expert advisory board. Since it launched in 2017, LBCA has been committed to raising awareness of the distinct aspects of invasive lobular carcinoma (ILC) and promoting ILC research. While ILC is the second most common histological breast cancer type representing 15% of breast cancer diagnoses in the United States annually, it is understudied compared to the more common invasive ductal carcinoma (IDC). ILC tumor cell density and lack of desmoplastic stromal reaction can pose challenges to detection by physical examination and mammography. Many studies have shown decreased accuracy of breast imaging tools for ILC, and those with ILC are often diagnosed at later stages and require more extensive surgery. We sought to hear from members of the LBCA community with ILC about their experiences with detection of their tumors. Methods: LBCA conducted an anonymous survey online. A link to the survey on the SurveyMonkey platform was made available for two weeks in June. It was sent to LBCA newsletter subscribers and posted to the LBCA website and ILC social media groups. The survey questions included stage and size of tumors at initial diagnosis and after surgery, and questions related to imaging for advanced ILC. It specifically asked whether and what type of mammogram initially detected the ILC. Results: Within 24 hours over 1,000 people responded, and a total of 1,476 people previously diagnosed with ILC responded by survey close. The majority of participants, 1,052 (72%), were from the US, followed by participants from 35 additional countries. 170 (12%) reported having metastatic ILC. 1,035 (70%) of respondents were under 60 at diagnosis. Of respondents reporting tumor size and stage, 936 (67%) of respondents indicated having a tumor larger than 2cm at diagnosis, and 897 (63%) reported stage 2 or higher, including 73 (5%) reporting stage 4 at initial diagnosis. In the subset of participants initially diagnosed with stage 2 or higher, 410 (46%) of respondents reported the tumor was not detected by mammogram. In the subset of participants who noticed changes in their breasts prior to the diagnosis, 521 (79%) had tumors larger than 2cm, and 490 (74%) were diagnosed at stage 2 or higher. Of the 1,241 respondents who had no preoperative therapy, 531 (43%) had tumors larger than initially seen on imaging and/or 321 (26%) had more tumors than initially found on imaging. Discussion: To the best of our knowledge this represents the largest survey seeking to understand patients’ experience with imaging to diagnose or visualize ILC. The results from this community survey of patients diagnosed with invasive lobular carcinoma confirmed patients’ perceptions of mammography as an imperfect screening tool to detect ILC. Of note were the findings that mammography failed to visualize 46% of ILC cases at stage 2 or higher, and the majority of respondents had tumors diagnosed/detected at stage 2 or higher and at sizes greater than 2cm. Moreover, participants often reported that the actual tumor size on the final pathology specimen was larger than seen on diagnostic imaging, and a significant number of respondents were diagnosed de novo metastatic. In summary, our findings affirm patients’ perception about the limitations of diagnostic and monitoring imaging of ILC. Our impressively large response also demonstrates the urgent need from patients’ perspectives for more research on better methods for detecting and monitoring ILC to improve outcomes for patients diagnosed with lobular disease.
 Citation Format: Laurie B Hutcheson, Janice Axelrod, Colleen L Fitzwater, Maxine S Jochelson, Gitte H Joergensen, Theresa Langdon, Julia K Levine, Otto Metzger, Mason Mitchell-Daniels, Barbara F Neilsen. Imaging and invasive lobular carcinoma: A survey study conducted by the lobular breast cancer alliance [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-15-03.

Maxine S. Jochelson

Papers

Exploring the added clinical value of breast MRI after contrast-enhanced spectral mammography in patients with invasive lobular carcinoma

Preoperative Immune Checkpoint Inhibition and Cryoablation in Early-Stage Breast Cancer

Reply to "Factors That May Influence Contrast-Enhanced Digital Mammography Findings".

Editorial: CONTRAST MAMMOGRAPHY-A PROMISING TOOL FOR THE PRE-OPERATIVE EVALUATION OF LOBULAR BREAST CANCER

Abstract P3-15-03: Imaging and invasive lobular carcinoma: A survey study conducted by the lobular breast cancer alliance