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Treatment and Survival Among Patients With Colorectal Cancer in Sub-Saharan Africa: A Multicentric Population-Based Follow-Up Study

Lucia Hämmerl, Nikolaus C.S. Mezger, Tobias P. Seraphin, Walburga Yvonne Joko-Fru, Mirko Griesel, Jana Feuchtner, Franck Gnahatin, Freddy Houéhanou Rodrigue Gnangnon, Nathan Okerosi, Phoebe Mary Amulen, Rolf Hansen, Margaret Ziona Borok, Carla Carrilho, Brahima Mallé, Clausina Ahoui Apendi, Nathan G. Buziba, Edom Seife, Biying Liu, Rafael Mikolajczyk, Donald M. Parkin, Eva J. Kantelhardt, and Ahmedin Jemal

Background: The burden of colorectal cancer (CRC) is increasing in Sub-Saharan Africa (SSA). However, little is known about CRC treatment and survival in the region. Methods: A random sample of 653 patients with CRC diagnosed from 2011 to 2015 was obtained from 11 population-based cancer registries in SSA. Information on clinical characteristics, treatment, and/or vital status was obtained from medical records in treating hospitals for 356 (54%) of the patients (“traced cohort”). Concordance of CRC treatment with NCCN Harmonized Guidelines for SSA was assessed. A Cox proportional hazards model was used to examine the association between survival and human development index (HDI). Results: Of the 356 traced patients with CRC, 51.7% were male, 52.8% were from countries with a low HDI, 55.1% had colon cancer, and 73.6% were diagnosed with nonmetastatic (M0) disease. Among the patients with M0 disease, however, only 3.1% received guideline-concordant treatment, 20.6% received treatment with minor deviations, 31.7% received treatment with major deviations, and 35.1% received no treatment. The risk of death in patients who received no cancer-directed therapy was 3.49 (95% CI, 1.83–6.66) times higher than in patients who received standard treatment or treatment with minor deviations. Similarly, the risk of death in patients from countries with a low HDI was 1.67 (95% CI, 1.07–2.62) times higher than in those from countries with a medium HDI. Overall survival at 1 and 3 years was 70.9% (95% CI, 65.5%–76.3%) and 45.3% (95% CI, 38.9%–51.7%), respectively. Conclusions: Fewer than 1 in 20 patients diagnosed with potentially curable CRC received standard of care in SSA, reinforcing the need to improve healthcare infrastructure, including the oncology and surgical workforce.

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Understanding Cancer Risk—Genes Matter!

Margaret Tempero

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BRAF/MEK Inhibition as a Bridge to Immunotherapy for Symptomatic BRAF V600 Melanoma Brain Metastases: A Case Series

Jacob Strelnikov, Alice Zhou, Omar Butt, Michael Ansstas, and George Ansstas

Targeted and immune therapies have changed the paradigm of treatment for patients with metastatic melanoma. Treatment of patients with symptomatic melanoma brain metastases, however, is complicated by the frequent use of immune suppression for the management of vasogenic edema and the urgency in addressing disease burden. Use of BRAF/MEK inhibitors in patients with a corresponding BRAF V600 mutation often results in rapid response but is hindered by high rates of disease relapse and progression. Immunotherapy has higher durability of response, but the rate of response is slower and responses can be significantly diminished for patients on concurrent steroid therapy. Considering this gap in evidence-based guidance for optimal adjuvant therapy sequence in immunosuppressed patients with BRAF V600–mutant melanoma brain metastases, we report on 4 cases utilizing BRAF/MEK inhibitors as a bridging therapy for brain metastases management before initiation of immune checkpoint inhibitor therapy. Future prospective studies will be required to determine the optimal treatment sequencing for patients in this population with high unmet medical need.

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Hormone Receptor–Positive Breast Cancer Sensitive to Pembrolizumab: Evidence of the Pathogenicity of the MLH1 Variant 1835del3

Henry G. Kaplan, Jeffrey R. Whiteaker, Brianna Nelson, Richard G. Ivey, Travis D. Lorentzen, Uliana Voytovich, Lei Zhao, David J. Corwin, Robert Resta, and Amanda G. Paulovich

A woman with estrogen/progesterone receptor–positive, ERBB2-negative metastatic breast cancer developed progressive disease despite treatment with multiple hormonal and chemotherapeutic modalities. She carried a germline variant of MLH1 (1835del3), also known as c.1835_1837del and v612del, the pathogenicity of which has not been conclusively determined. MLH1 staining was not seen on immunohistochemical staining of her tumor tissue. The patient experienced a >5-year dramatic response to 4 doses of pembrolizumab. Family studies revealed multiple other relatives with the MLH1 1835del3 variant, as well as multiple relatives with colon cancer. The one relative with colon cancer who underwent genetic testing demonstrated the same variant. Laboratory studies revealed that the patient’s tumor showed loss of heterozygosity (LOH) in the MLH1 region, high levels of microsatellite instability, and a high tumor mutational burden. LOH in the MLH1 region, along with the remarkable clinical response to pembrolizumab treatment and the presence of the same MLH1 variant in affected relatives, supports the hypothesis that the MLH1 1835del3 variant is pathogenic. Given the patient’s family history, this likely represents an uncommon presentation of Lynch syndrome. Physicians should be alert to evaluate patients for targetable genetic variants even in unlikely clinical situations such as the one described here.

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Molecular Classification Improves Therapeutic Options for Infants and Young Children With Medulloblastoma

Aditi Bagchi, Sandeep K. Dhanda, Paige Dunphy, Edgar Sioson, and Giles W. Robinson

Medulloblastoma in infants and young children is a major challenge to treat because craniospinal irradiation (CSI), a cornerstone of therapy for older children, is disproportionately damaging to very young children. As a result, trials have attempted to delay, omit, and replace this therapy. Although success has been limited, the approach has not been a complete failure. In fact, this approach has cured a significant number of children with medulloblastoma. However, many children have endured intensive regimens of chemotherapy only to experience relapse and undergo salvage treatment with CSI, often at higher doses and with worse morbidity than they would have initially experienced. Recent advancements in molecular diagnostics have proven that response to therapy is biologically driven. Medulloblastoma in infants and young children is divided into 2 molecular groups: Sonic Hedgehog (SHH) and group 3 (G3). Both are chemotherapy-sensitive, but only the SHH medulloblastomas are reliably cured with chemotherapy alone. Moreover, SHH can be molecularly parsed into 2 groups: SHH-1 and SHH-2, with SHH-2 showing higher cure rates with less intensive chemotherapy and SHH-1 requiring more intensive regimens. G3 medulloblastoma, on the other hand, has a near universal relapse rate after chemotherapy-only regimens. This predictability represents a significant breakthrough and affords oncologists the ability to properly risk-stratify therapy in such a way that the most curative and least toxic therapy is selected. This review examines the treatment of medulloblastoma in infants and young children, discusses the molecular advancements, and proposes how to use this information to structure the future management of this disease.

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Volume 21 (2023): Issue 8 (Aug 2023)

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Adolescent and Young Adult (AYA) Oncology, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology

Smita Bhatia, Alberto S. Pappo, Melissa Acquazzino, Wendy A. Allen-Rhoades, Marie Barnett, Scott C. Borinstein, Robert Casey, Sun Choo, Rashmi Chugh, Shira Dinner, Ralph Ermoian, Douglas Fair, Noah Federman, Jeanelle Folbrecht, Shipra Gandhi, Julie Germann, Robert Goldsby, Robert Hayashi, Alex Y. Huang, Mary S. Huang, Linda A. Jacobs, Cathy Lee-Miller, Michael P. Link, John A. Livingston, Maryam Lustberg, Marcio Malogolowkin, Kevin C. Oeffinger, Christine A. Pratilas, Damon Reed, Jodi Skiles, Margaret von Mehren, Nicholas Yeager, Sarah Montgomery, and Lisa Hang

This selection from the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology focuses on considerations for the comprehensive care of AYA patients with cancer. Compared with older adults with cancer, AYA patients have unique needs regarding treatment, fertility counseling, psychosocial and behavioral issues, and supportive care services. The complete version of the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology addresses additional aspects of caring for AYA patients, including risk factors, screening, diagnosis, and survivorship.

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Being Sick Isn’t Easy

Margaret Tempero

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Changes in Prescribing Patterns in Stage III Colon Cancer

Fang-Shu Ou, Daniel J. Walden, Joseph J. Larson, Sandra Kang, Cassia R. Griswold, Benjamin E. Ueberroth, Bhamini Patel, Amber Draper, Puneet Raman, Olatunji B. Alese, Mohamad B. Sonbol, Tanios S. Bekaii-Saab, Christina S. Wu, and Daniel H. Ahn

Background: For patients with resected stage III colon cancer, 6 months of adjuvant fluoropyrimidine-based chemotherapy has been the standard of care. The IDEA collaboration aimed to evaluate whether 3 months of adjuvant chemotherapy was noninferior to 6 months. Despite failing to meet its primary endpoint, the subgroup analyses demonstrated noninferiority based on regimen and treatment duration when a risk-stratified approach was used. Patients and Methods: To evaluate the impact of the results of the IDEA collaboration, we evaluated adjuvant chemotherapy prescribing practice patterns, including planned adjuvant treatment regimen and duration from January 1, 2016, to January 31, 2021. The time period was selected to evaluate chemotherapy prescribing patterns prior to the abstract presentation of the IDEA collaboration in June 2017 and after full manuscript publication in March 2018. Results: A total of 399 patients with stage III colon cancer who received adjuvant chemotherapy were included in the analysis. A significant increasing trend for use of 3 months of adjuvant chemotherapy was observed after presentation of the IDEA abstract (P<.001). A significant change in CAPOX (capecitabine/oxaliplatin) prescribing was also observed, increasing from 14% of patients prior to presentation of the IDEA abstract to 48% after presentation (P<.001). Comparing 3 months of CAPOX with 6 months of FOLFOX (fluorouracil/leucovorin/oxaliplatin), 3 months of CAPOX use also steadily increased over time (adjusted odds ratio [aOR], 1.28; 95% CI, 1.20–1.37; P<.001). Among subgroups of interest, no differences in adoption of CAPOX were observed. The adoption of 3 months of CAPOX was similar in patients with low-risk cancer (aOR, 1.27; 95% CI, 1.17–1.37) and those with high-risk cancer (aOR, 1.31; 95% CI, 1.16–1.47). Conclusions: Despite the IDEA collaboration failing to demonstrate noninferiority of 3 months’ duration of adjuvant therapy compared with 6 months, the findings have influenced practice prescribing patterns, favoring CAPOX and a shorter duration of planned adjuvant treatment.

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Compound Kushen Injection Reduces Severe Toxicity and Symptom Burden Associated With Curative Radiotherapy in Patients With Lung Cancer

Jie Liu, Qingxi Yu, Xin Shelley Wang, Qiuling Shi, Jun Wang, Fan Wang, Simeng Ren, Jiayue Jin, Baojin Han, Wenzheng Zhang, Xueyao Su, Shuanghu Yuan, and Hongsheng Lin

Background: Radiotherapy (RT) causes adverse events for which there are no effective treatments. This study investigated the clinical benefits of compound Kushen injection (CKI) in managing radiation injury in patients with lung cancer. Methods: A multicenter, open-label, randomized clinical trial randomly assigned patients with lung cancer to receive either CKI (20 mL/d for at least 4 weeks) integrated with curative RT (RT + CKI group; n=130) or RT alone (control group; n=130). The primary outcome was the incidence of grade ≥2 radiation-induced lung injury (RILI) in the lungs, esophagus, or heart. Secondary outcomes included patient-reported symptoms, quality of life, objective response rate (ORR), and toxic effects. Results: During the 16-week trial, the RT + CKI group had a significantly lower incidence of grade ≥2 RT-related injury than the control group (12.3% [n=16] vs 23.1% [n=30]; P=.02). Compared with the control group, the RT + CKI group experienced a significant decrease in moderate-to-severe symptoms of fatigue, cough, and pain (P<.001 for the treatment and time interaction term); significantly less physical symptom interference (P=.01); and significantly better quality of life by the end of the trial (P<.05). No statistically significant difference in ORR was found. Adverse reactions associated with CKI were rare. Conclusions: This study demonstrated low toxicity of CKI and its effectiveness in patients with lung cancer in reducing the incidence of grade ≥2 RILI and symptom burden, improving patients' quality of life.