 suggested that adolescent and young adult (AYA) patients treated for acute myeloid leukemia (AML) have a high risk of developing long-term health complications.

The most common complications, or late effects as they are referred to in the study, observed among AYA survivors in this study were cardiovascular, endocrine, and respiratory diseases. Moreover, these complications were found to be more prevalent among non-white AYA patients and those living in more impoverished communities.

“Our study shed light on the high burden of late effects among young survivors of AML,” lead author Renata Abrahão, MD, MSc, PhD, a postdoctoral fellow at the UC Davis Comprehensive Cancer Center and the Center for Healthcare Policy and Research, said in a press release.

To estimate the cumulative incidence and investigate the main predictors of late effects among this patient population, researchers identified 1168 eligible AYAs with AML who survived at least 2 years after diagnosis from 1996 to 2012 in the California Cancer Registry. Importantly, late effects were reported from State hospital discharge data, and patients were followed through 2014.

Ultimately, the most common late effects reported at 10 years after diagnosis were endocrine (26.1%), cardiovascular (18.6%), and respiratory (6.6%), followed by neurologic (4.9%), liver/pancreatic (4.3%), renal (3.1%), avascular necrosis (2.7%), and second primary malignancies (2.4%). Moreover, of the total study cohort, 547 (46.8%) received a hematopoietic stem cell transplant (HSCT).

Following multivariable adjustments, the investigators found that AYAs who underwent HSCT or had non-favorable risk AML experienced an approximately 2-fold or higher increased likelihood of all late effects. Additionally, AYAs of Hispanic, Black, or Asian/Pacific Islander race or ethnicity and those who resided in lower socio-economic neighborhoods were shown to be at higher risk of numerous late effects when compared with non-Hispanic White patients.

“This higher risk may relate to the financial hardship that patients with cancer often experience,” senior author Theresa Keegan, PhD, MS, associate professor at the UC Davis Comprehensive Cancer Center, said in a press release. “As a result of cancer, AYA survivors and their families may miss work, experience income loss, and incur substantial out-of-pocket expenses.”

According to the researchers, many factors may have led to the observed disparities in disease burden. These include differences in therapeutic management, patient’s response to treatment, AML with high-risk mutations, coexisting diseases, and socioeconomic factors.

Further, compared to younger or older cancer survivors, the investigators indicated AYA patients suffer a higher financial burden. They may go without treatment and long-term follow-up visits that could mitigate the impact of late effects. Moreover, their risk of late effects may be exacerbated by unhealthy lifestyle habits such as smoking, excessive alcohol consumption, lack of exercise, non-protected sun exposure, and poor diet.

“Our findings underscore the need for long-term surveillance for the prevention, early detection and treatment of late effects, and can inform the development of AYA-focused consensus-based guidelines that will ultimately improve the quality of life and survival of these young vulnerable patients,” the study authors wrote.

1. Abrahão R, Huynh JC, Benjamin DJ, et al. Chronic medical conditions and late effects after acute myeloid leukaemia in adolescents and young adults: a population-based study. 

2. Young survivors of acute myeloid leukemia have long-term complications from treatment [news release]. Published November 9, 2020. Accessed November 17, 2020. https://www.newswise.com/articles/young-survivors-of-acute-myeloid-leukemia-have-long-term-complications-from-treatment?sc=sphr&xy=10019792

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These results suggested that adolescent and young adult patients treated for acute myeloid leukemia have a high risk of developing long-term health complications.

Study Suggests AYAs Treated for AML Have High Risk of Developing Long-Term Complications

Response-based consolidation involved-field radiation therapy (IFRT) appears to be a safe and effective standard of care for a cohort of pediatric patients with high-risk classical Hodgkin lymphoma (cHL), with very low rates (2.4%) of failures outside of these modern risk-adapted radiation treatment volumes observed.

Additionally, PET2 positivity did not appear to identify the majority of all relapse sites. These findings were presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting and are part of a phase 3 study from the Children’s Oncology Group.

“These results validate that modern combined modality efforts of chemotherapy and radiation therapy for pediatric patients with Hodgkin lymphoma is very effective and leads to excellent outcomes,” lead study investigator Rahul R. Parikh, MD, director of the Laurie Proton Therapy Center at Robert Wood Johnson University Hospital and associate professor of radiation oncology at Rutgers Robert Wood Johnson Medical School, said in a press release.

From December 2009 to January 2012, 164 evaluable patients 22 years old or younger with stage IIIB (43%) and stage IVB (57%) were eligible for the study. In total, 85 (51.5%) patients presented with a large anterior mediastinal mass, 44 (26.7%) with extra-mediastinal bulk, and 85 (51.5%) with macronodular splenic involvement. Overall, bulk disease was observed in 138 (84%) patients.

Patients were categorized as rapid early responders (RER) or slow early responders (SER) following 2 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC). The SER patients were randomized to 2 additional chemotherapy cycles of ifosfamide/vinorelbine and 2 cycles of ABVE-PC, followed by adapted IFRT to areas of bulky disease and/or slow-responding site(s). RER patients underwent 2 additional ABVE-PC cycles and involved-site radiation therapy (ISRT) to sites of initial bulky involvement only.

Ultimately, 125 (76%) patients received radiation therapy (RT). Sixty of the 125 were RER and 65 were SER.

Of note, per protocol specifics, no patients received a boost beyond the prescribed 21 Gy. Relapses were characterized with respect to site (initial, new, or both; and initial bulk or initial non-bulk), and radiation field (in-field, out-of-field, or both).

At a median follow-up of 4.5 years, 27 of 145 (19%) patients relapsed and 23 patients were evaluable. Of those 23 patients, 11 were RER patients and 12 were SER patients. Moreover, within the 23 evaluable patients with relapse (all but 1 received protocol IFRT), there were 105 total sites (median = 4; range, 1-11) of relapse.

Further, 64% of relapses occurred within an initial site of involvement, including 18% that were at an initial site of bulky disease, 32% which occurred in a new site of disease (that would not have been covered by RT), and 2.4% (occurring in 3 RER and 1 SER) which were isolated out-of-field relapses that would have been covered by historical IFRT.

Overall, 94% of relapses occurred in sites that were initially PET2-negative.

1. Parikh RR, Hoppe BS, Hodgson D, et al. Patterns of Relapse from a Phase 3 Study of Response-Based Therapy for High-Risk Hodgkin Lymphoma (AHOD0831): A Report from the Children’s Oncology Group. Presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting. Abstract #: 

2. Studying Patterns of Relapse in Pediatric Hodgkin Lymphoma using a Response-Based Therapy Approach [news release]. New Brunswick, NJ. Published October 23, 2020. Accessed November 9, 2020. https://www.newswise.com/articles/studying-patterns-of-relapse-in-pediatric-hodgkin-lymphoma-using-a-response-based-therapy-approach?sc=sphr&xy=10021790

A study presented at ASTRO suggested that response-based consolidation involved-field radiation therapy appears to be a safe and effective standard of care for a cohort of pediatric patients with high-risk classical Hodgkin lymphoma.

IFRT Appears Safe, Effective Standard of Care for Some Pediatric Patients with High-Risk cHL

suggested that improvements in the delivery of surgery and equal utilization of definitive radiation therapy are at least partially responsible for closing the survival gap between African American and Caucasian patients with early-stage non-small cell lung cancer (ES-NSCLC).

However, though Black patients are now more likely to receive the most effective treatment compared to a decade ago, the disparity for this patient population persists.

“We wanted to take a closer look at surgery – the most effective therapy – and how the 2 other second-line treatment options might affect the disparities in long-term outcomes across populations,” senior author Olugbenga Okusanya, MD, an assistant professor of Surgery at Thomas Jefferson University and researcher at the Sidney Kimmel Cancer Center – Jefferson Health, said in a press release.

 “There has been concern that these second-line treatments have been contributing to the disparity in outcomes.”

The most effective treatment for ES-NSCLC is surgery to remove a portion of lung. However, 2 types of radiation therapy are also used as a second-line therapy, with stereotactic ablative radiotherapy (SABR) shown to be more effective than external beam radiation therapy (EBRT) for early-stage disease.

Using the National Cancer Database, researchers queried for African American and Caucasian patients diagnosed with clinical stage I NSCLC between 2004 and 2015. Trends in surgery, SABR, or EBRT were then compared using Kaplan-Meier and Cox hazards models. Overall, 174,338 (90.6%) patients identified were Caucasian and 18,077 (9.4%) were African American.

“Few reports have included this many patients and looked at both surgery and radiation therapy,” Okusanya noted.

African American patients were found to be less likely to receive surgery (60.3% vs. 66.9%; 

 < .001) and more likely to receive EBRT (12.4% vs. 10.6%; 

 < .001); however, there was no significant difference in rates of SABR (8.8% vs. 9.2%; 

 = .066). Importantly, from 2004 to 2015, the surgery rates increased for African American patients from 44.4% to 61.8% and for Caucasian patients from 57.6% to 65.6%.

Even with the increase observed in surgery rates, African American patients had worse 5-year overall survival on an unadjusted analysis (46.7% vs. 47.9%; 

 = .009). Ultimately though, when adjusted for definitive treatment, African American patients did have improved survival (HR, 0.97; 95% CI, 0.94-0.99).

Of note, other studies have suggested that comorbidities in Black patients were one of the drivers for worse outcomes, rather than the utilization of surgery.

“In contrast, we found that when Black patients get surgery there is actually a trend for them to have better survival than their white counterparts,” Okusanya said.

“We need to continue to reduce barriers to successful treatments for Black cancer patients,” added Okusanya. “We know these disparities exist across cancer types and treatments and understanding some of the drivers of these inequities is key to fixing them.”

1. Lutfi W, Martinez-Meehan D, Sultan I, et al. Racial disparities in local therapy for early stage non‐small‐cell lung cancer. 

2. Racial Disparities in Treatment for Common Lung Cancer Persist Despite Gains [news release]. Philadelphia. Published October 28, 2020. Accessed November 19, 2020. https://www.newswise.com/articles/racial-disparities-in-treatment-for-common-lung-cancer-persist-despite-gains?sc=dwhr&xy=10019792

Though researchers found that Black patients with early-stage non-small cell lung cancer are now more likely to receive the most effective treatment compared to a decade ago, the disparity for this patient population persists.

Study Finds Racial Disparities in ES-NSCLC Persist Despite Gains in Treatment

HPV16-L1 DRH1 epitope-specific antibodies are linked to HPV16-induced malignant disease, according to results from a multicenter European study published in 

These findings are based on a highly specific diagnostic test that appears to indicate cancer and predict its course from just a pinprick of blood. The newly developed HPV16-L1 DRH1 epitope-specific serological assay detects levels of DRH1 to HPV16.

Importantly, HPV16 is the most carcinogenic of the 206 HPV-subtypes identified thus far and accounts for up to 90% of HPV-induced cancer deaths.

“This is the first time that we have been able to show a link between raised levels of this specific antibody and HPV cancers, indicating the course of disease,” Thomas Weiland, MD, of the division of General Otorhinolaryngology in Austria’s Medical University of Graz, said in a press release.

 “This might raise the potential of being able to detect disease recurrence much earlier than current clinical practice.”

This multicenter study was comprised of 1486 patients, including 301 patients with head and neck squamous cell carcinoma (HNSCC), 12 with HIV-positive anal cancer, 80 who were HIV-positive, 29 who were vaccinated with Gardasil-9, and 1064 healthy controls. Participants were tested for human HPV16-L1 DRH1 antibodies using the DRH1-competitive-serological-assay.

Ultimately, the DRH1-competitive-serological-assay demonstrated a sensitivity of 95% (95% CI, 77.2%-99.9%) for HPV16-driven HNSCC, and 90% (95% CI, 55.5%-99. 7%) for HPV16-induced anal cancer in HIV-positive patients. Moreover, overall diagnostic specificity was 99.46% for men and 99.29% for women 30 years or older.

Following HPV vaccination, the observed antibody level increased from an average of 364 ng/ml to 37,500 ng/ml. During post-therapy monitoring, patients with HNSCC showing an antibody decrease in the range of 30% to 100% lived disease free over a period of up to 26 months. Of note, the increase of antibodies from 2750 ng/ml to 12,000 ng/ml mirrored recurrent disease.

In addition, the investigators were also able to show that the L1-capsid protein is expressed in HPV16-DNA positive tumor-tissue.

“While HPV infection does not indicate cancer, scientists have suspected for some time that if antibodies were to develop, there may be a link to cancer,” Ralf Hilfrich, PhD, founder of Abviris and the creator of the DRH1 blood-based HPV tumor marker, said in the release. “Being able to detect that early enough could have a major impact on patient outcomes.”

“The test’s specificity has enabled scientists to show that rising levels of HPV antibodies in blood do reflect malignancy,” Hilfrich added. “The study also indicates that it may prove diagnostically significant, compared to current detection methods, when a biopsy is hard to access, or where the site of the primary cancer is unknown or unidentifiable, such as very early metastasis.”

Overall, these study results provide promising findings, especially when compared to the most effective cancer screening test so far, the Pap-smear, which has significantly reduced the incidence of HPV-induced cervical cancer, even with less impressive key data of about 50% sensitivity and 98% specificity.

1. Weiland T, Eckert A, Tomazic PV, et al. DRH1 – a novel blood-based HPV tumour marker. 

2. ‘Pinprick’ biomarker blood test offers diagnostic potential in HPV-related cancers Study shows rising antibody levels predict the course of cancer [news release]. Ahrensburg, Germany. Published November 11, 2020. Accessed November 18, 2020. https://www.newswise.com/articles/pinprick-biomarker-blood-test-offers-diagnostic-potential-in-hpv-related-cancers-study-shows-rising-antibody-levels-predict-the-course-of-cancer?sc=dwhr&xy=10019792

“This might raise the potential of being able to detect disease recurrence much earlier than current clinical practice,” said Thomas Weiland, MD.

Biomarker Blood Test Offers Diagnostic Potential for HPV-Related Cancers

Researchers at Mount Sinai have shown that early CT screening for lung cancer leads to early diagnosis and treatment, thus saving lives.

However, Mount Sinai researchers also identified racial disparities in the diagnosis of early-stage lung cancer. Given that diagnosing lung cancer in its early stages can lead to successfully eliminating lung cancer with surgery alone, the importance of closing this observed disparity gap is critical.

, Emanuela Taioli, MD, PhD, director of the Institute for Translational Epidemiology at Mount Sinai, discussed the racial disparities in the diagnosis of early-stage lung cancer that she and her colleagues identified as well as programs that have been initiated to help close this disparity gap.

This segment comes from the CancerNetwork® portion of the MJH Life Sciences Medical World News, airing daily on all MJH Life Sciences channels.

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Given that diagnosing lung cancer in its early stages can lead to successfully eliminating lung cancer with surgery alone, the importance of closing this disparity gap is critical.

Emanuela Taioli, MD, PhD, on Disparities in Early-Stage Lung Cancer Diagnosis

Adagrasib (MRTX849) demonstrated an acceptable safety profile and promising clinical activity in pretreated patients with non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and other solid tumors with a 

 mutation, according to results from the multi-cohort phase 1/2 KRYSTAL-1 study presented at the 32nd EORTC-NCI-AACR Symposium on Molecular Targets and Therapeutics.

Adagrasib works by irreversibly and selectively binding to the 

 mutation in its inactive state, blocking its ability to send cell-growth signals and leading to cancer cell death. The mutation occurs in approximately 14% of lung adenocarcinomas, the most common subtype of NSCLC, 3% to 4% of colorectal cancers, and 2% of pancreatic cancers, which translates into more than 100,000 people each year worldwide.

In this study, adagrasib was evaluated in patients with advanced or metastatic solid tumors harboring a 

 mutation previously treated with chemotherapy and anti-PD-1/PD-L1 therapy. In dose expansion, a dose of 600 mg twice daily was assessed and established as the recommended phase 2 dose.

The primary end points of the study include safety, pharmacokinetics, clinical activity, and efficacy. Exploratory objectives include evaluation of pharmacodynamic biomarkers and correlation of molecular markers with antitumor activity.

Regarding patients with NSCLC, as of August 30, 2020, 79 patients (57% female; median age, 65 years [range, 25-85]; 22%/78% ECOG PS 0/1) with pretreated NSCLC were treated with 600 mg of adagrasib twice daily in phase 1/1b (n = 18) or a phase 2 (n = 61) cohort.

 Among 51 patients evaluable for clinical activity (14 from phase 1/1b and 37 from phase 2), 45% of patients had an objective response; this included 5 patients who had an unconfirmed partial response (PR) and remain on treatment. The disease control rate was 96%.

Among the 14 patients evaluable for clinical activity from phase 1/1b with longer follow-up, the confirmed objective response rate (ORR) was 43% and the majority of patients with responses (4/6) have had treatment ongoing for over 11 months. The median time on treatment was 8.2 months (range, 1.4-13.1+).

The most commonly reported (>20%) treatment-related adverse events (TRAEs) in patients with NSCLC included nausea (54%), diarrhea (48%), vomiting (34%), fatigue (28%), and increased alanine aminotransferase (ALT; 23%). Moreover, the only commonly reported (>2%) grade 3 or 4 serious TRAE was hyponatremia (3%).

 patients are a population for which there are no proven targeted therapies. Once chemotherapy or immune therapy fails in a patient, treatment options are limited,” Pasi A. Jänne, MD, PhD, director of the Lowe Center for Thoracic Oncology at Dana Farber Cancer Institute, said in a press release. “The fact that we are seeing responses in 45% of patients with adagrasib is incredibly meaningful as it opens up the possibility of a new treatment option for this subset of lung cancer patients.”

As of the same data cutoff date, preliminary safety data are available for 31 patients treated with 600 mg of adagrasib twice weekly in phase 1/1b (CRC, n = 2) and select phase 2 cohorts (CRC, n = 22; other solid tumors, n = 7).

 For all 31 patients, baseline characteristics included median age of 63 years (range, 25-80), 45% female, and 29%/71% with ECOG PS of 0/1, respectively.

Of the evaluable patients with CRC, 17% (3/18) had a confirmed objective response and 2 of the 3 patients remain on treatment. Disease control was also observed in 94% (17/18) of patients and 12 of the 18 patients remain on treatment.

Moreover, 6 patients in the other solid tumor cohort were evaluable for clinical activity. Confirmed PRs were observed in 1 patient with endometrial cancer and 1 patient with pancreatic cancer; unconfirmed PRs were also observed in 1 patient with ovarian cancer and 1 with cholangiocarcinoma. Further, 2 patients with appendiceal cancer who were treated achieved stable disease. All 6 of these patients remain on treatment.

Regarding safety, the most commonly reported (>20%) TRAEs in patients with CRC or other solid tumors included diarrhea (58%), nausea (52%), fatigue (42%), and vomiting (36%).

Of note, researchers are also looking at combining adagrasib with other targeted therapies moving forward, such as pembrolizumab (Keytruda) for NSCLC, cetuximab (Erbitux) for CRC, the investigational SHP-2 inhibitor TNO-155 in either NCSLC or CRC, and afatinib for NSCLC.

1. Targeted inhibitor of mutated KRAS gene shows promise in early trial for lung, bowel, and other solid tumors [news release]. Published October 24, 2020. Accessed November 19, 2020. https://www.newswise.com/articles/targeted-inhibitor-of-mutated-kras-gene-shows-promise-in-early-trial-for-lung-bowel-and-other-solid-tumors?sc=sphr&xy=10021790

2. Jänne PA, Rybkin II, Spira AI, et a. KRYSTAL-1: Activity and Safety of Adagrasib (MRTX849) in Advanced/Metastatic Non–Small-Cell Lung Cancer (NSCLC) Harboring KRAS G12C Mutation. Presented at the 32nd EORTC-NCI-AACR Symposium on Molecular Targets and Therapeutics. Abstract #: 

3. Johnson ML, Ou SHI, Barve M, et al. KRYSTAL-1: Activity and Safety of Adagrasib (MRTX849) in Patients with Colorectal Cancer (CRC) and Other Solid Tumors Harboring a KRAS G12C Mutation. Presented at the 32nd EORTC-NCI-AACR Symposium on Molecular Targets and Therapeutics. Abstract #: 

Adagrasib demonstrated an acceptable safety profile and promising clinical activity in pretreated patients with non-small cell lung cancer, colorectal cancer, and other solid tumors with a KRAS G12C mutation.