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|Year : 2021 | Volume
| Issue : 2 | Page : 312--314
News from the world of oncology
|How to cite this article:|
. News from the world of oncology.Indian J Cancer 2021;58:312-314
|How to cite this URL:|
. News from the world of oncology. Indian J Cancer [serial online] 2021 [cited 2021 Oct 21 ];58:312-314
Available from: https://www.indianjcancer.com/text.asp?2021/58/2/312/317900
Adjuvant nivolumab in resected esophageal cancer
Neoadjuvant chemoradiotherapy (NACRT) or neoadjuvant chemotherapy (NACT) followed by surgery is currently the standard of care for patients with resectable, locally advanced esophageal or gastroesophageal (GE) junction cancer. However, risk of cancer recurrence remains high in these patients especially in those with less than pathological complete response. Adjuvant treatment is definitely needed for these subset of patients but has seldom shown benefit and most patients are put on surveillance. Nivolumab has improved outcomes in advanced unresectable and chemorefractory recurrent Esophageal and GE junction carcinoma.
A global, randomized, double-blind, placebo-controlled phase 3 trial (CheckMate 577) was recently published by Kelly RJ et al in the New England Journal of Medicine which looked at adjuvant nivolumab in this setting (Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer, https://www.nejm.org/doi/full/10.1056/NEJMoa2032125). Adults with resected (R0) stage II or III esophageal or GE junction cancer who had received NACRT and had residual pathological disease were randomized to receive nivolumab at 240 mg every 2 weeks for 16 weeks, followed by 480 mg every 4 weeks or a matching placebo for a maximum of one year. The primary end-point was disease-free survival (DFS).
This was a planned interim analysis done at 24 months, which showed a median DFS of 22.4 months versus 11.0 months among patients who received nivolumab versus placebo respectively. This was statistically significant with a 31% reduction in the risk of recurrence and death with nivolumab. The hazard ratios for recurrence and death favoured nivolumab across most pre-specified subgroups and irrespective of tumor-cell PD-L1 expression. Both distant and loco-regional recurrences were lower in the nivolumab group (29% versus 39% and 12% versus 17% respectively). The magnitude of benefit in DFS was greater where nivolumab was initiated at least 10 weeks after surgery than in those where it was initiated less than 10 weeks after surgery. Cause for this is unknown and may require further studies.
Grade 3 or 4 adverse events of any cause occurred in about a third patients in both arms. Serious adverse events leading to discontinuation were more common in nivolumab group (9% versus 3%). However the safety profile of nivolumab was similar to that seen in other types of solid tumors.
There are limited data regarding the role of adjuvant immunotherapy in patients receiving perioperative regimen like FLOT (5-fluouracil, docetaxel and oxaliplatin) followed by surgery with residual disease and in those patients receiving definitive chemoradiotherapy. Ongoing trials are aimed at addressing these questions.
Access to immunotherapy may be limited in low and middle income countries due to the cost associated with the treatment and real world data on use of immune checkpoint inhibitors in India in solid tumors shows the use is limited to less than 2%.
However, the results of this study are promising showing a doubling of DFS in a disease where most patient would succumb to their illness. Checkmate 577 could be a practice changing therapeutic option for these patients.
ORCID iD: https://orcid.org/0000-0002-6710-6067
Obesity in childhood brain tumor survivors associated with hypothalamic-pituitary dysfunction
Childhood brain tumor survivors (CBTS) are at a high-risk for obesity due to multitude of disease and treatment related factors. Weight gain during childhood could lead to cardiovascular complications later in life. This may be related to underlying disorders of the hypothalamic-pituitary axis (HPD). Hence, early diagnosis and intervention is necessary in these patients.
A nationwide retrospective study by Schaik J et al. (High prevalence of weight gain in childhood brain tumor survivors (CBTS) and its association with hypothalamic-pituitary dysfunction, https://doi.org/10.1200/JCO.20.01765) was published in the Journal of Clinical Oncology. For the study, the data was collected from 7 centers in the Netherlands. Children diagnosed with brain tumors in a period from 2002 to 2012, who had survived for at least 2 years after diagnosis, were studied. Children with craniopharyngioma or pituitary tumors were excluded as many would be having tumor related obesity. Patients with BMI follow up data of minimum 6 months after diagnosis were included. Data related to tumor and treatment along with anthropometric measurements and endocrine parameters (to identify hypothalamic pituitary disorders) was collected retrospectively.
Significant weight gain was considered as an increase in body mass index (BMI) >+2.0 standard deviation score. BMI >2 and BMI>3 were taken as overweight and obese respectively. The data was assessed separately for normal weight and underweight children at diagnosis as underweight children would have undergone certain weight improving interventions to support treatment. A total of 661 CBTS were assessed with a mean follow-up of 7.3 years. Of the 602 CBTS without underweight at diagnosis, 11.6% developed significant weight gain, while this was seen in 68% of underweight CBTS (n= 32). After a mean follow-up time of 7.8 years, 20.3% were found to be overweight and 8.5% were classified as obese. The proportion of overweight was higher when compared to the general population.
Increase in BMI may be an indicator of underlying hypothalamic pituitary dysfunction. In the 661 CBTS studied, 22.8% had one or more hypothalamic pituitary disorder at follow-up with a mean time of 3 years from diagnosis.
The following parameters were associated with weight gain: high BMI at diagnosis, low grade glioma (especially suprasellar location), presence of diabetes insipidus and central precocious puberty during follow-up.
The study had certain limitations. Being retrospective in nature, the parameters assessed were not done uniformly as there was no standardized protocol for surveillance till recently. Investigations may have been need-based and were more likely to be done in severely affected children. This could possibly lead to an underestimation of endocrine disorders. Moreover as BMI does not distinguish between fat and muscle mass, prospective studies with involvement of bioimpedance would be ideal.
In conclusion this study did show a high prevalence of weight gain in CBTS which could reflect HPD. These patients should receive endocrine surveillance and support for weight disorders in their follow up.,
ORCID iD: https://orcid.org/0000-0002-2272-8065
Barriers to patient agreement for participation in cancer clinical trials
Clinical trials are a crucial component in the research, development and evaluation of safer and more efficacious treatment strategies. For patients, these are the few ways to get a new or experimental approach before it is approved for general use. Still, almost 39% of trials are terminated prematurely due to lack of accrual of required patient population. This is because only 5-8% of adult cancer patients enroll in clinical trials, even though 70% of them are estimated to be inclined to participate in clinical trials.
A meta-analysis of 13 studies (8883 patients) identified barriers to trial participation. In their analysis, 56% of patients were unable to participate due to non-availability of studies for their cancer type or stage. Of the remaining, 22% did not meet eligibility criteria and 15% who were eligible did not enroll (Systematic review and meta-analysis of the magnitude of structural, clinical, and physician and patient barriers to cancer clinical trial participation; https://doi.org/10.1093/jnci/djy221).
The present study published in the Journal of National Cancer Institute by Unger et al (“When Offered to Participate”: A systematic review and meta-analysis of patient agreement to participate in cancer clinical trials, https://doi.org/10.1093/jnci/djaa155), answered a highly pertinent question about the actual rate of participation among patients who are given an opportunity to participate in a clinical trial. This was a systematic review and meta- analysis of studies that evaluated the participation to cancer treatment or cancer control trials conducted in the United States and published between 2000 and 2020. Studies must have documented the number of patients who were offered trial participation and those who enrolled in the same.
Out of the 4073 studies flagged by the 3 search engines (PubMed, Web of Science, and Ovid Medline databases), 35 studies comprising of 9759 patients met the inclusion criteria. Overall participation rate in trials with either treatment or cancer control was 55.0%.
There were no statistically significant differences in trial participation rates between studies that required patient consent compared with those that did not (59.9% versus 52.0%; p=0.17). Similarly, no differences in trial participation between prospective and retrospective study designs (51.7% versus 58.1%; p=0.26), or those studies based on patient report as against physician or staff report (65.7% versus 53.6%; p=0.16) was noted. There was also no difference in enrollment rates between different races (Black, Hispanic, Asian versus White). Trial participation rates were statistically significantly higher at academic centers than community centers (58.4% versus 45.0%; p = 0.04). The most common reasons of non-enrollment were patients' desire to control their treatment choice, by avoiding participation where treatment may be randomly assigned and avoiding protocol treatment side effects.
This review indicates that patients, when offered to participate in a clinical trial would likely choose to do so more than half the time, irrespective of race, ethnicity, or study design. The main reason for low trial participation rates may be related to the structural and clinical barriers associated with enrollment in a study, rather than patient disinterest. Research and policies to improve trial participation may focus more on these issues for improving recruitment.
ORCID iD: https://orcid.org/0000-0002-6686-8860