Introduction

Distress is defined by the National Comprehensive Cancer Network (NCCN) as “a multifactorial unpleasant emotional experience of a psychological (cognitive, behavioral, emotional), social, and/or spiritual nature that may interfere with the ability to cope effectively with cancer, its physical symptoms, and its treatment.”1 About 30 to 50% of newly diagnosed and recurrent cancer patients show a significant level of distress.23 While cancer-related distress is often amenable to treatment, it is frequently underdiagnosed and thus undertreated, with less than 10% of patients receiving psychosocial help.4 An elevated level of distress is associated with poor health-related quality of life (QoL), poor compliance to treatment, decreased patient satisfaction with medical care, and possibly reduced survival. It is now being recognized as the sixth vital sign of cancer care.35678 The NCCN distress thermometer (DT) is the most widely used tool to screen and quantify distress.9

Head and neck cancer (HNC) patients experience elevated levels of distress compared with other patients with significant distress reported in 30 to 56% of patients at diagnosis.51011121314 Multiple factors associated with higher distress in HNC include the sociodemographic profile, the disease site, the stage at diagnosis, the treatment received, the inability to perform activities of daily living, and the response to treatment.1115 While most of these factors remain unmodifiable, psychosocial counselling has been shown to significantly alleviate distress levels and improve physical, mental, and emotional well-being. A pretreatment and during-treatment visit to a qualified counsellor can potentially reduce posttreatment distress, improve treatment compliance, and improve outcomes.16

We conducted this randomized trial to assess the impact of psychosocial counselling in HNC cancer patients undergoing radiation therapy (RT).

Materials and Methods

Results

Between February 2016 to May 2017, 600 patients were screened, and 212 patients (n = 108 STD, n = 104 INV) were accrued (Fig. 1). The primary reason for screen failure was patients not meeting the inclusion criteria (n = 210 had a DT less than 4 at baseline, n = 28 were unable to fill the questionnaires, n = 10 had a synchronous/metachronous primary). For the primary endpoint evaluation at 6 months after completion of RT, 90 (83.3%) patients were evaluable in the STD arm and 89 (85.5%) patients in the INV arm.

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Fig. 1: Consolidated Standards of Reporting Trials diagram of the study. INV, Intervention arm; STD, Standard arm.

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The demographic and disease profile of patients in both arms are given in Table 1. The majority of the patients were male (81.13%) and were married (92.9%). Most patients had a prior history of tobacco use (55.1%) and belonged to a low socioeconomic background (66.4%). The oral cavity (58%) was the most common primary site, and adjuvant RT (63.2%) was the most common indication for RT. Overall, 52.8% of patients received concurrent chemotherapy. There was no significant difference between any disease/demographic parameters between the two arms.

The proportion of patients with significant distress at 6 months' posttreatment completion were 9% (n = 8) in STD arm versus 15.6% (n = 14) in INV arm, p = 0.20. At 6 months' posttreatment completion, the median distress score was 2 (interquartile range [IQR]: 2–3) in both arms. There was no significant difference in scores in any of the domains of the NCCN distress checklist score (Table 2, Fig. 2A and B).

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Fig. 2: (A) Distress problem checklist scores at baseline between two arms. (B) Distress problem checklist scores at 6-month follow-up between two arms. INV, Intervention arm; STD, Standard arm.

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There was no significant difference in the two arms for any symptoms (ESAS) at baseline or 6 months (Fig. 3A and B).

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Fig. 3: (A) Edmonton Symptom Assessment Score (ESAS) at baseline between two arms. (B) ESAS at 6-month follow-up between two arms. INV, Intervention arm; STD, Standard arm.

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There was no significant difference in the two arms for the global QoL or any domains: physical, emotional, cognitive, social, or role functioning (Table 3).

Survival Outcomes

At a median follow-up of 39 months (IQR:16–53 months), there was no difference in STD arm versus INV arm for 3-year disease-free survival: 55.4% (95% confidence interval [CI]: 45.2–65.6) versus 57.3% (95% CI: 46.9–67.7), p = 0.78 and for 3-year overall survival: 73.4% (95% CI: 64–82.8) versus 72% (95% CI: 62.6–81.4), p = 0.63 (Fig. 4A and B).

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Fig. 4: (A) Disease-free survival of the two arms. (B) Overall survival of the two arms. INV, Intervention arm; STD, Standard arm.

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Discussion

In this randomized trial, psycho-oncology/palliative/supportive care counselling did not significantly impact the distress levels of the patient posttreatment. For the secondary outcomes, the intervention did not demonstrate any significant benefit over the prevailing standard of care, i.e., assessment/counselling by the treating oncologist symptom-directed pharmacological interventions and referral.

Distress is a complex phenomenon with many factors responsible for cancer-induced distress. In a report by Lewis et al, on HNC patients receiving RT, a low socioeconomic status (p = 0.04), presence of proliferative growth at presentation (p = 0.008), site of the tumor (oral cavity, p = 0.02), comorbidity (p = 0.04), and presence of Ryle's tube or tracheostomy tube at baseline (p = 0.01) were predictors of distress.11 However, only the patient's socioeconomic status was significant for higher distress levels in the multivariable analysis. Other factors that have been implicated for cancer-induced distress include marital status, gender, education level, tobacco usage, and age. Psychosocial counselling has shown to mitigate some of these risk factors, albeit many of these factors are interrelated, and any intervention for reducing cancer-induced distress will have to address several if not all these factors. While psychosocial/pharmaceutical/surgical interventions can address many factors like pain and cosmetic disfigurement, the sociodemographic causes of distress remain largely unmodifiable. Financial toxicity of loss of employment, cancer treatment, and resulting disability has been associated with significant distress in multiple studies.2223 While similar conclusive data are lacking from a resource-limited setting, the financial toxicity associated with cancer treatment is likely to be a significant cause of concern in this setting.242526

The reason for no significant improvement in distress scores with psychosocial/supportive care interventions in our trial can be possibly attributed to the prevalence of many nonmodifiable factors leading to distress. Unlike the West, tobacco remains the primary driver of a higher incidence of HNC incidence in India.27 Head–neck squamous cell carcinomas in India and most other low- or middle-income country are primarily a disease of low socioeconomic status and are associated with a lack of social support, lower education levels, and lack of employment.28 These significant contributors to distress are unlikely to be mitigated by psycho-oncology counselling, and supportive measures. Recently, a randomized trial to ascertain the impact of (early palliative care [EPC]) referral in advanced HNC was reported from India by Patil et al. The authors reported that more than 40% of patients received financial aid in each arm. Similar to the results of our trial, there was no significant impact on the QoL (FACT HN score p = 0.94), ESAS score, and survival.29 The negative results of these two trials probably point toward the contribution of nonmodifiable background factors, more than the disease itself, to cancer-associated deterioration in QoL and anxiety.

While patient-reported outcomes (PROs) remain a valuable tool for assessing an intervention's efficacy, there is an element of uncertainty about the generalizability and reliability of PROs. PROs are impacted by other factors such as coping skills, education levels, and priorities.3031 Multiple randomized trials have reported discordance between the patient-reported and physician-reported outcomes.102932

We used a cut of ≥4 for clinically significant distress as per the NCCN 2013 guidelines. However, distress score cut values vary between primary disease sites, race, ethnicity, country, and socioeconomic profile.9 It is plausible that the cutoff value for significant distress could have been different for the patient population included in this trial, i.e., only HNCs (with a majority being oral cancers) from India.

A similar approach, EPC has improved survival outcomes and QoL in patients with advanced/metastatic tumors of the lung, gastrointestinal tract, and head–neck region.333435 In head–neck patients treated with curative intent, at least two randomized trials have shown the benefit of psychological/supportive care interventions. In a randomized trial by Krebber et al, patients of head–neck and lung cancer with untreated distress were randomized to standard of care and stepped-up care (comprising of watchful waiting, guided self-help, problem-solving therapy, and psychotherapy and/or psychotropic medication).12 The recovery rate was better in the stepped care arm at 6 months (55 vs. 29%) and 12 months (46 and 37%). In another randomized trial reported from China in patients undergoing curative-intent RT, patients who received psychosocial interventions (n = 89) during RT had an improvement in depression (p < 0.05), anxiety (p < 0.05), and overall health-related QoL (p < 0.05).36

In this randomized trial, neither the patient nor the physician was blinded to the treatment allocation. Also, most trials showing a benefit of palliative care/psycho-oncology referrals are in the palliative setting where patients are rarely assessed and treated by all oncology specialties, i.e., surgical, medical, and radiation oncologists. The majority (nearly 60%) of the patients included in this trial included patients who received trimodality therapy. It is plausible that symptoms like pain could have been managed by the oncologists themselves. As per our institutional data, only 5 to 10% patients require dedicated pain care referral for patients receiving Chemoradiation (CTRT). These factors could have contributed to patients receiving adequate psychosocial care by the treating physician(s) themselves in our trial.

One of the strengths of this study lies in the fact that the trial included only patients with significant distress at baseline as has been recommended in multiple previous reports.2137 A relatively large number (n = 212) of patients were accrued from within a reasonable time. The attrition rate in the trial for the evaluation of the primary endpoint was acceptable in both arms. The cancer treatment protocols were uniform throughout the study. The patients were assisted in filling the questionnaires by trained nursing staff. Another strength of the study was evaluating multiple aspects of psychological well-being, including distress, QoL, and symptom burden.

The primary weakness of the study comes from the fact that there was a gross mismatch between the anticipated distress at 6 months and the actual results. The reasons for the same have been highlighted above. Baseline assumptions in similar future trials should be based on reports from the population where the study is planned rather than extrapolation from a population with a different sociodemographic profile. Another contentious issue can be the time point posttreatment (6 months) for estimating distress as the primary endpoint. This was chosen as some patients with head–neck cancers suffer from acute toxicities for as long as 3 months' posttreatment. A time point of 6 months will possibly limit the impact of acute toxicities on distress levels in the two arms. There is a shortage of dedicated manpower for supportive services like pain management/palliative care in many cancer centers in developing and underdeveloped countries. A referral to dedicated supportive care clinics is likely to be a human resource intensive exercise. In our opinion, a sustained benefit for a period of at least 6 months' post-RT could justify a routine incorporation of this approach into clinical practice. However, we accept that the results of the study could have been changed if an endpoint of DS at 3 months or earlier was chosen. Finally, this trial had most patients who received RT post-surgical excision. While we have used surgical excision as a stratification variable, it may be possible that results may be possibly different in a cohort of patients who are treated with definitive RT/CTRT.

Psychosocial and supportive interventions are likely to impact certain cancer patients' psychosocial health positively. However, a dedicated psychosocial referral for all patients in routine clinical practice is resource-intensive in human resources and finances. Hence, future trials should include a larger pool of patients across cancer sites and further focus on identifying suitable patients to make this approach more pragmatic and cost-effective. A reasonable step forward is utilizing a combination of sensitive screening methods that incorporate psychological health parameters, the sociofinancial condition of the patient, the caregiver support, and other logistic issues like transport/lodging.3839 Furthermore, while holistic palliative care services cater well to the neediest patient population, i.e., palliative intent patients, perhaps an individualized supportive care approach may be better suited for curative intent patients. Referrals (as per the initial patient assessment) to dedicated pain clinic physicians, psychiatrists, medical social workers, and financial counsellors can be a more resource-sparing and cost-effective approach for such patients.40 The World Health Organization rehabilitation 2030 goal also emphasizes developing a robust multidisciplinary rehabilitation workforce suitable for country context and promoting rehabilitation concepts across all health workforce education.41

Conclusion

To summarize, this trial did not find any significant benefit of early integration of psychosocial/palliative/supportive care on the distress levels, symptom burden, QoL, or survival in HNC patients undergoing curative-intent RT at 6 months' posttreatment completion. The primary treating physician should continue to assess and intervene for the patients' distress and other psychological needs. Referral to psychosocial/palliative and other supportive care services should be individualized for each patient after screening and ascertaining the main symptom burden of the patient.