Journal Article Annotations
2023, 2nd Quarter

Psychooncology

Annotations by Christian Bjerre Real, MD, MMCI, Deepti Chopra, MBBS, MPH, Daniel McFarland, MD, Marie Tobin, MD, Barbara Lubrano di Ciccone, MD.
July, 2023

Efficacy of exercise interventions for women during and after gynaecological cancer treatment – a systematic scoping review.
Black women’s distress matters: Examining gendered racial disparities in psycho‐oncology referral rates.
Efficacy of Olanzapine in Addition to Standard Triplet Antiemetic Therapyfor Cisplatin-Based ChemotherapyA Secondary Analysis of the J-FORCE Randomized Clinical Trial.

PUBLICATION #1 — Psychooncology

Efficacy of exercise interventions for women during and after gynaecological cancer treatment – a systematic scoping review.

Grace Laura Rose, Elizabeth Mary Stewart, Briana Kristine Clifford, Tom George Bailey, Alexandra Jane Rush, Claudia Rose Abbott, Sandra Christine Hayes, Andreas Obermair, Alexandra Leigh McCarthy.

Abstract: Support Care Cancer. 2023 May 17;31(6):342. doi: 10.1007/s00520-023-07790-8.

Purpose:
To systematically synthesise evidence of exercise intervention efficacy for physical/psychosocial outcomes that matter to women during/following treatment for gynaecological cancer.

Methods:
Five databases were searched (PubMed, EMBASE, CINAHL, PsychInfo, Scopus). Exercise-only intervention studies that included women during/ following treatment for any gynaecological cancer, with/ without control comparison, on any physical or psychosocial outcome(s), were included and qualitatively appraised using the Revised Cochrane Risk of Bias tool and a modified Newcastle-Ottawa Scale.

Results:
Seven randomised controlled trials (RCTs), three single-arm pre-post studies, and one prospective cohort study satisfied were included (11 studies). Most studies were completed following treatment (91%), included combined (aerobic and resistance; 36%) and aerobic (36%) training, were fully/mostly (63%) unsupervised, and had a moderate-to-high risk of bias. Overall, 33 outcomes (64% objectively-measured) were assessed. Improvements were observed in aerobic capacity (V̇O₂ Peak +1.6 mL/kg/min, 6-minute walk distance +20-27 m), lower- (30-second sit-to-stand +2-4 repetitions) and upper-limb strength (30-second arm curl +5 repetitions; 1RM grip strength/chest press +2.4-3.1 kg), and agility (timed up-and-go -0.6 seconds). However, changes in quality of life, anthropometry/body composition, balance and flexibility were inconsistent. There was no evidence to support worsening of outcomes.

Conclusion:
Preliminary research into the role of exercise post-gynaecological cancer suggests an improvement in exercise capacity, muscular strength, and agility which, in the absence of exercise, typically decline following gynaecological cancer. Future exercise trials involving larger and more diverse gynaecological cancer samples will improve understanding of the potential and magnitude of effect of guideline-recommended exercise on outcomes that matter to patients.

Annotation

Findings:

The finding:
Rose et al., systematically reviewed effects of exercise interventions in patients undergoing and immediately after gynecological cancer treatment. They found that exercise programs help with improvement in physical strength, mobility and help maintain activities of daily living, which may influence quality of life (QOL). Effects on QOL and mental well-being were mixed.

Strength and weaknesses:
Exercise interventions have been extensively studied in breast, prostate, and colorectal cancer, so focusing on gynecological cancers is a strength of this paper. Additional strengths are that a majority of their findings are supported by level II evidence and that the effect of exercise on fatigue is reviewed. The discussion the safety of such interventions and how difficult it is study the influence of exercise prescription on outcomes. One notable limitations of this article is that the median sample size of studies was 35, which likely influenced many outcome measures. Overall, it is a nicely written paper.

Relevance:
Exercise oncology promotes regular activity; however, exercise has only been studied in limited cancer types, and there are no specific guidelines for creating a rehabilitation program for patients undergoing cancer treatment. Understanding the effect of exercise on various cancer types may help shape rehabilitation program for patients and improve adjustment during or after cancer treatment.

PUBLICATION #2 — Psychooncology

Black women’s distress matters: Examining gendered racial disparities in psycho‐oncology referral rates.

Arwa Aburizik, Madeline Brindle, Ebonee Johnson, Alyssa Provencio, Martin Kivlighan, Brandon LeBeau.

Abstract: Psychooncology. 2023 Jun;32(6):933-941. doi: 10.1002/pon.6134. Epub 2023 Apr 19.

Objective:
Presently, there is a lack of research examining gendered racial disparities in psycho‐oncology referral rates for Black women with cancer. Informed by intersectionality, gendered racism, and the Strong Black Woman framework, this study sought to examine the possibility that Black women are adversely affected by such phenomena as evidenced by lower probability of being referred to psycho‐oncology services compared to Black men, White women and White men.

Methods:
Data for this study consisted of 1598 cancer patients who received psychosocial distress screening at a comprehensive cancer center in a large Midwest teaching hospital. Multilevel logistic modeling was used to examine the probability of referral to psycho‐oncology services for Black women, Black men, White women, and White men while controlling for patient‐reported emotional and practical problems and psychosocial distress.

Results:
Results indicated that Black women had the lowest probability of being referred to psycho‐oncology services (2%). In comparison, the probability of being referred to psycho‐oncology were 10% for White women, 9% for Black men, and 5% for White men. Additionally, as nurses’ patient caseload decreased, the probability of being referred to psycho‐oncology increased for Black men, White men, and White women. In contrast, nurses’ patient caseload had little effect on the probability of being referred to psycho‐oncology for Black women.

Conclusions:
These findings suggest unique factors influence psycho‐oncology referral rates for Black women. Findings are discussed with particular focus on how to enhance equitable care for Black women with cancer.

Annotation

The finding:
In this study, Aburizik et al., found that Black women have a significantly lower probability of being referred to psycho-oncology services. Black women had significantly lower odds of referral to psycho-oncology services compared to White men, White women, and Black men combined. When compared with a higher caseload, a lower nurse caseload was associated with increased referral to psycho-oncology services for White men, White women, and Black men. In contrast, for Black women, the effect of caseload on referral to psycho-oncology services was not significant.

Strength and weaknesses:
Mortality rates for Black women with cancer, especially breast cancer, exceed their racial and ethnic counterparts. A strength of this study is the evaluation of the negative impact of combined sexism and racism on the treatment of psychosocial distress as measured by referral rates to psycho-oncology services. Additionally, the study employed matching techniques and considered many covariables to address the relatively small number of Black cancer patients. A weakness of the study is the failure to identify the reasons for non-referral even in the case of high reported psychosocial distress. For example, some patients may have declined referral to psycho-oncology services.

Relevance:
By examining the impact of gendered racial disparities on one aspect of cancer care, this study highlights several important needs: the need for education to address provider implicit bias, the need to develop a thoughtful and deliberate system of referral to psycho-oncology services, and the need to address the role of gendered racial disparities in healthcare inequity.

PUBLICATION #3 — Psychooncology

Efficacy of Olanzapine in Addition to Standard Triplet Antiemetic Therapyfor Cisplatin-Based ChemotherapyA Secondary Analysis of the J-FORCE Randomized Clinical Trial.

Masakazu Abe, Takuhiro Yamaguchi, Yukiyoshi Fujita, Tomoyasu Nishimura, Koichi Kitagawa, Naoki Inui, Katsuya Hirano, Yukio Sakata, Hirotoshi Iihara, Yuichi Shibuya, Kenichi Suzuki, Kazuhiko Shibata, Kensuke Hori, Haruko Daga, Toshiaki Nakayama, Yasuhiko Sakata, Takako Yanai Takahashi, Sadamoto Zenda, Hironobu Hashimoto.

Abstract: JAMA Netw Open. 2023 May 1;6(5):e2310894.

Importance:
It is unknown whether olanzapine combined with triplet antemetic therapy is effective for all patients undergoing highly emetogenic chemotherapy. A secondary analysis of randomized clinical trials using olanzapine may provide insight into the effectiveness of olanzapine for chemotherapy-induced nausea and vomiting (CINV), including cisplatin.

Objective:
To examine the add-on effect of olanzapine according to risk factors for CINV.

Design, setting, and participants:
This preplanned secondary analysis evaluated results of the J-FORCE trial, a large double-blind, placebo-controlled phase 3 randomized clinical trial conducted in Japan from February 9, 2017, to July 18, 2018. Participants were enrolled from 26 participating hospitals across Japan and included patients aged 20 to 75 years who had a malignant tumor and were cisplatin-naive. The efficacy analysis population of the J-FORCE trial was analyzed according to allocation adjustment factors (sex [male or female], age [≥55 years or <55 years], and cisplatin dose [≥70 mg/m2 or <70 mg/m2]) and patient-related risk factors (history of motion sickness, drinking habit [defined as alcoholic drinks consumption in excess of occasional drinking], and history of morning sickness during pregnancy). Statistical analysis was performed from February 18 to April 18, 2020.

Interventions:
Patients were randomized 1:1 to receive 5 mg of olanzapine or placebo combined with standard triplet antiemetic therapy.

Main outcomes and measures:
The primary end point was complete response (CR, defined as no vomiting and no use of rescue medication) in the delayed phase (24-120 hours after cisplatin-based chemotherapy administration). Secondary end points were CR, complete control, and total control in the acute, delayed, and overall phases for 6 CINV risk factors as well as time to treatment failure. The CR point estimates and 95% CIs of the differences between groups were calculated, and a Mantel-Haenszel test was performed.

Results:
Of the 705 patients (mean [SD] age, 63.0 [9.2] years; 471 males [66.8%]) included in the efficacy analysis population; 581 patients (82.4%) were 55 years or older, and 526 (74.6%) were treated with a cisplatin dose of 70 mg/m2 or more. Risk difference (RD) for a CR in the delayed phase was significantly greater in the olanzapine group than the placebo group in males (RD, 12.6% [95% CI, 5.0%-20.1%]; P = .001); in females (RD, 14.5% [95% CI, 2.2%-26.3%]; P = .02); in those 55 years or older (RD, 11.1% [95% CI, 3.9%-18.2%]; P = .003) or younger than 55 years (RD, 23.6% [95% CI, 7.3%-38.3%]; P = .005); for a cisplatin dose of 70 mg/m2 or more (RD, 13.5% [95% CI, 5.9%-21.0%]; P < .001); for those without a history of motion sickness (RD, 13.9% [95% CI, 6.9%-20.6%]; P < .001); for those with a drinking habit (RD, 14.9% [95% CI, 6.1%-23.4%]; P = .001) or without a drinking habit (RD, 12.0% [95% CI, 2.5%-21.3%]; P = .01); and for those with a history of morning sickness during pregnancy (RD, 27.2% [9.7%-42.6%]; P = .002). In other subgroups, a delayed CR was higher in the olanzapine group than the placebo group, although not significantly higher.

Conclusions and relevance:
Results of this study suggest a benefit of using 5 mg of olanzapine plus triplet antiemetic therapy to counter CINV regardless of the presence or absence of risk factors.

Conclusions:
Metformin use may lower the risk of delirium and mortality in DM patients.

Annotation

The finding:
This is a secondary analysis of a large phase 3 randomized trial, J-FORCE, that demonstrated efficacy of olanzapine to prevent nausea and vomiting in patients receiving highly emetogenic chemotherapy (e.g., high dose cisplatin or anthracycline) when given alongside a standard prophylactic anti-emetic regimen of three medications. This secondary analysis found that olanzapine was beneficial for preventing chemotherapy induced nausea and vomiting regardless of any additional features that might make the patient particularly susceptible to nausea and vomiting including sex, age, cisplatin dose, history of motion sickness, a habit of imbibing alcohol, or a history of nausea and vomiting with pregnancy for several days after given chemotherapy.

Strength and weaknesses:
This was a randomized trial with the endpoint of efficacy defined as no use of rescue medications from 24-120 hours after chemotherapy. The secondary analysis reviewed issues related to predisposition to nausea and vomiting from chemotherapy. This is an important point because one may question the use of adding olanzapine for all patients receiving highly emetogenic chemotherapy due to its side effect profile. This secondary analysis was not powered to definitively answer these questions.

Relevance:
The use of olanzapine as an anti-nausea medicine in the setting of chemotherapy should be well understood by C-L psychiatrists who may be asked to weigh in its use. As non-psychiatric clinicians become increasingly comfortable using this psychotropic, C-L psychiatrists should guide oncologists in its use.