Commentary

First postulated with radiobiological calculation by Withers et al., in 1988[1], accelerated repopulation of tumor clonogen is a valid contributor to our inability to cure cancers. He had demonstrated that the clonogen doubling time of a head and neck squamous cell carcinoma (HNSCC) may reduce from an average of 60 days to an estimated average of about 4 days, beyond 25 days, amounting to a daily increase in TCD50 of about 0.6 Gy. The clinical implication of the same has been studied subsequently. Rosenthal[2] has documented that the 5-year survival was 5.8% for patients with treatment breaks of more than 1 week compared with 11.4% for those without.

In a survey done by the Royal College of Radiologists (RCR),[3] it was found that 63% of patients treated with curative radiotherapy (RT) have one or more treatment interruptions. The most common cause of the same was stated as public holidays (39%) followed by machine breakdown (35%). Patient unwillingness and unauthorized interruptions accounted for only 4% of the total interruptions, whereas radiotherapy reactions accounted for 8% of the breaks. Split course RT regimens definitely show poorer control rates. Uncompensated interruption of a single day causes loss of local control by 1–1.4%.[2] Timing of the interruption also has an impact on the outcome due to accelerated repopulation after approximately the 28^th day of radiotherapy. Herrmann et al.,[4] correlated overall survival (OS) with the timing of treatment break. They showed that when there were no breaks, the survival was 61%, with the survival being 65% with breaks during first 3 wks, 25% for breaks during the middle 2 wks, and 18% with breaks during the last 2 wks of treatment.[4]

We commend the authors for their work[5] in this direction and especially in the Indian setting and in HNSCC, which comprises almost 50% of the cancer load in most radiotherapy centers in the country. This has relevance to a commonly encountered but important clinical issue. Recognition of factors responsible for interruptions would not only provide a reason for the inferior controls but would also help identify factors that could be modified. This would be useful in identifying factors distinct to our country or a particular region. This would have administrative, logistic and policy implications. The authors have taken an innovative approach to analyze this important situation. They have evaluated the component of unauthorized interruptions, the “defaulters”. These amounted to 23.4% of total patients (76 of 324), a value significantly higher than that documented in the RCR survey value of 4%. This, they concluded was attributable to the challenging socioeconomic background (difficult to modify) as well as the lack of awareness (a modifiable factor) about the potential deleterious effects of interruptions among the patients. Faith in traditional healers as stated by the authors may also be contributory. In the Indian setting where logistic issues abound, proper evaluation of the contributory factors is an important step to instituting interventions to prevent the same.

The authors have not enlisted the demographic profile of the analyzed patients, which would have helped to pursue insights regarding the outcomes.

They have documented the socioeconomic factors leading to treatment default, however, correlation of the interruptions, if any, to treatment induced toxicities (grade wise, recorded before the point of default) would have helped in identifying the possible role of the oncologist in preventing the default, by pre-empting and managing toxicities effectively. It may be logical to conclude that patients who have logistic issues responsible for non-compliance, when faced with treatment induced toxicities would have a higher number of treatment breaks. Another effective intervention would be the use of the telephone, when available or home visits by medical social workers/volunteers or local health workers, especially for patients undergoing radical treatments.

In their analysis, treatment with RT alone or Concurrent Chemoradiation (CTRT) was not found to have any significant impact on treatment interruption. In patients treated with CTRT, toxicities are definitely higher (mainly mucositis and myelosuppression) and could lead to more treatment interruptions compared to RT alone. This is supported by data from the study by Rosenthal (43% vs 34% rates of mucositis). The lack of association in the present study may be due to the fact that they have not taken into consideration the interruptions advised by the oncologist and also the small numbers.

Patients with stages IV-A/B had a greater likelihood of being non-compliant to treatment in their study. The greater baseline symptomatology due to higher stage of disease could be further aggravated by RT induced mucositis.

The authors have also documented the rates of relapse in relation to occupation. This could be a reflection of socioeconomic factors rather than the occupation itself.

The RCR survey suggests that routine departmental audits would be an effective method to recognize and pick up interruptions early and would also ensure that there would be no interruption exceeding 2 days for at least 95% of the total treated patients. Cordial support from the technologist as well as engineers for minimization of machine breakdown is important. They suggest radiobiological correction only after failure to correct other technico-logistic measures namely alternate machine, compensatory weekend treatment.

In the Indian setting, provision of domiciliary facilities for patients receiving radical intent RT could be an effective option especially in patients who may not comply to treatment for reasons related to distance, difficult terrain and similar logistic issues. Regular on-treatment reviews, audits and support group meetings involving the treating oncologist, nurses, nutritionist, occupational therapist to counsel and manage the toxicities are a few effective measures to reduce interruptions. Proper evaluation of psychosocial parameters and socio-economic conditions are also vital to successful completion of planned treatment.

It would be interesting to assess the impact of such interventions in dealing with treatment related non-compliance, especially for patients undergoing curative intent treatment. Even in patients undergoing palliative RT, it could lead to the genesis and implementation of effective, short course RT schedules. These steps would have far reaching implications in countries like ours where more than 50% of the patient population with not only HNSCC but other common cancers are socioeconomically disadvantaged. Invention stems out of necessity and there is definitely a need to device strategies to identify, prevent and correct factors that lead to “unauthorized” treatment interruptions.