|Year : 2017 | Volume
| Issue : 1 | Page : 262-266
Palliative thoracic radiotherapy in advanced lung cancer: A single institution experience
C Hotwani1, JP Agarwal1, K Prabhash2, A Munshi1, A Joshi2, S Misra1, D Kumar1, S Das1, SG Laskar1
1 Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
2 Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
|Date of Web Publication||1-Dec-2017|
Prof. J P Agarwal
Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
BACKGROUND: Majority of patients of lung cancer present with locally advanced or metastatic disease, where systemic therapy is the treatment of choice. Many of these patients have local symptoms due to thoracic disease, wherein radiotherapy is proven to be an effective modality for alleviation of symptoms. However, the optimal dose of radiotherapy for adequate palliation remains debatable. The purpose of this retrospective study was to assess the efficacy of two different schedules of thoracic radiotherapy (TRT) with respect to symptom palliation. MATERIALS AND METHODS: A total of 100 consecutively treated patients with stages III-IV lung cancer treated with two different fractionation regimens of palliative TRT, either protracted course 20 Gy/5# over 1 week or short course of 17 Gy/2# over 8 days were assessed for symptom relief and survival. Impact of patient, tumor and treatment-related factors on response and overall survival (OS) was done by univariate analysis using log-rank test. RESULTS: Median age of the entire cohort was 60 years, majority being males, smokers with low Eastern Cooperative Oncology Group performance status (performance score ≥2). Predominant symptoms were chest pain (68) followed by cough (21) and dyspnea (15). Palliative TRT was offered as either protracted course 20 Gy/5# over 1 week or short course of 17 Gy/2# over 8 days in 21 and 79 patients respectively. Median duration of symptom relief was 2 months, no differences in OS at 1 year with either regimen. CONCLUSIONS: TRT is an effective means of palliation having similar symptom relief and outcomes with weekly (17 Gy/2# over 8 days) or protracted radiotherapy regimens (20 Gy/5#over 1 week). Short TRT schedules are convenient and economical for patients as well as resource sparing for high volume centers.
Keywords: Lung cancer, palliation, radiotherapy
|How to cite this article:|
Hotwani C, Agarwal J P, Prabhash K, Munshi A, Joshi A, Misra S, Kumar D, Das S, Laskar S G. Palliative thoracic radiotherapy in advanced lung cancer: A single institution experience. Indian J Cancer 2017;54:262-6
|How to cite this URL:|
Hotwani C, Agarwal J P, Prabhash K, Munshi A, Joshi A, Misra S, Kumar D, Das S, Laskar S G. Palliative thoracic radiotherapy in advanced lung cancer: A single institution experience. Indian J Cancer [serial online] 2017 [cited 2021 Jul 24];54:262-6. Available from: https://www.indianjcancer.com/text.asp?2017/54/1/262/219587
| » Introduction|| |
Lung cancer constitutes one of the most common malignancies worldwide. Majority of the patients present with advanced stage disease not amenable to curative treatment and are offered palliative radiotherapy or chemotherapy. Palliative thoracic radiotherapy (TRT) is effective for improving symptoms from intrathoracic tumor burden, such as hemoptysis, cough, chest pain, and dyspnea ,,, leading to improvement of quality of life in about one-third of patients.
In a review on the role of radiotherapy or chemotherapy in patients otherwise not fit for curative treatment, radiotherapy has been reported to have effective control of local symptoms especially for patients with poor performance status, old age, significant weight loss and patients who are less likely to tolerate chemotherapy. Palliative TRT essentially entails delivery of lesser total dose with a higher dose per fraction to a large volume disease so as to relieve localized symptoms. The optimal radiation schedule for palliation of these symptoms has not been determined, and it varies widely across the world. A survey of practice from one US radiation therapy (RT) center  reported that only 12% of lung cancer patients received low dose palliative RT, whereas a typical UK center would treat a greater proportion of patients in this manner. Commonly used fractionation include 30 Gy in 10 fractions, 8 Gy for two fractions with once weekly schedule or 20 Gy in 5 days at 4 Gy/fraction. Studies have used different dose-fractionation schedules with different total doses, expecting better and prolonged symptom relief with higher total dose and protracted fractionation. Fewer studies like Medical Research Council (MRC) 1992 and 1996 have shown better symptom relief with short course TRT., However, MRC 1996 study showed a survival advantage with protracted regimen in patients with good performance status. Another study comparing 17 Gy in two fractions versus 42 Gy in 15 fractions by Sundstrøm et al., did not show any benefit in the symptom relief and survival in the long treatment arm. There is no good evidence that higher doses of radiotherapy are more or less effective for symptom control than lower doses. A shorter course of hypofractionated radiation is an attractive option, given the regimen provides equivalent symptom relief and is not unduly toxic than protracted regimens.
The purpose of this retrospective study was to assess the efficacy of two different TRT regimens, short course regimen of 17 Gy/2# weekly and protracted course of 20 Gy/5# over 1 week, in locally advanced or metastatic patients of lung cancer presenting with localized symptoms and poor performance status.
| » Materials and Methods|| |
A hundred patients consecutively treated with palliative TRT having thoracic symptoms were included in the analysis. TRT was delivered using 6/15 MV photons with 2 cm margins around gross tumor volume. The two dose regimens were either short course hypofractionated regimen of 17 Gy given in two fractions over 1 week or protracted daily schedule of 20 Gy in five fractions over 1 week. The TRT schedule was primarily decided in the clinic taking into consideration various patient and disease-related factors such as a general condition, age, performance score (PS), disease volume, as well as the logistic issues. All the patients received adequate supportive care to manage their symptoms in the form of opioid analgesics, etc.
These patients were assessed for subjective relief of symptoms by using visual analog scale (VAS) 1 week after treatment and subsequently followed-up every 2/3 months or as required. Duration and extent of response in terms of predominant symptom relief was noted.
Predominant symptom relief or extent of response was correlated with various patient, tumor and treatment-related factors using Pearson's correlation with statistical significance of P ≤ 0.05. Overall survival (OS) was calculated as the period from the date of registration to the date of last follow-up or death due to any cause. The prognostic impact of various patient, tumor and treatment-related factors on response and OS was analyzed by univariate analysis and its significance was reported using log-rank test.
| » Results|| |
Median age of the entire group was 60 years (range 24–96 years) with 87% being males. Overall 52% were Eastern Cooperative Oncology Group PS ≥2 and 70% had some form of comorbidities. Most common symptom was chest pain (68%), followed by cough and dyspnea. Of all, 79% patients were treated with short course TRT (17 Gy/2#/8 days), whereas 21% patients received protracted course of radiotherapy (20 Gy/5#/1 week). Most common histology was squamous cell carcinoma (n = 42), followed by adenocarcinoma (n = 32). Metastatic disease at presentation was seen in 54% patients. Chemotherapy was received by 78% patients, most common regimens being platinum doublets with paclitaxel or gemcitabine. The patient, tumor and treatment details of these patients are shown in [Table 1].
In patients receiving a short course TRT, 69% patients had a parallel opposed beam arrangement with median treated area of 192 cm 2 [Table 2] while, in protracted course TRT, 50% had similar arrangement. Overall treatment was well tolerated with 91% completing the planned course of radiotherapy. Four patients did not complete the course of treatment as two of them died before completion due to disease and two patients had worsening of symptoms on treatment, leading to an unplanned conclusion of TRT.
Response to palliative TRT was known for 83 patients, as four patients could not complete planned treatment, 4 defaulted for palliative chemotherapy that was planned and 9 others were lost to follow-up after completion of TRT. Sixty-two percent (52/83) patients had ≥50% relief of symptoms after TRT. Median duration of symptom relief was 2 months that was similar in patients receiving short course TRT and those receiving fractionated regimen. However, the greater proportion of those patients receiving daily treatment experienced ≥50% symptom relief as compared to those receiving a short course TRT [82% vs. 57% respectively, [Table 3], P = 0.060]. On comparing chest pain versus other symptom relief, there was no significant difference in proportion of patients having ≥50% relief as well as the extent of symptom relief.
|Table 3: Correlation and univariate analysis between response to TRT and with patient, tumor and treatment related factors|
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On correlating extent of symptom relief with various patient, tumor and treatment-related factors, there was a trend toward significance for ≥ 50% relief with daily TRT [P = 0.060, [Table 3]. Other factors like PS, predominant symptom, histology or stage of disease did not have any significant impact on the extent of symptom relief. Predominant symptom was chest pain, which was relieved in 84% patients, extent of response ranging from 0 to 100% (median 50%).
At a median follow-up of 5 months (interquartile range [IQR 02–12 months), median OS in these patients was 7 months (IQR 3–13 months) and actuarial OS at 1 year was 34.5%. On univariate analysis, younger age had better OS (P = 0.039). No statistical significant difference was seen in OS of patients receiving different TRT regimens. Patients with metastatic or localized presentation also did not have statistical significant differences in OS [Table 3] and [Figure 1]a,[Figure 1]b,[Figure 1]c.
|Figure 1: Kaplan–Meier curve showing overall survival comparing, (a) patients with age <60 years versus those ≥60 years, (b) M0 versus M1 disease at presentation, (c) short course thoracic radiotherapy (TRT) versus protracted course of TRT|
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| » Discussion|| |
Lung cancer patients commonly presenting in locally advanced or metastatic stage are treated with palliative intent and significant proportion of these patients have local symptoms that require treatment. Commonly presenting symptoms include cough, chest pain, hemoptysis, breathlessness, etc., Many of these symptoms are relieved by TRT. However, the extent of symptom relief provided by radiotherapy as assessed by clinician as well as reported by patients remains subjective and hence is crude method. MRC trials involved assessment of palliation by clinicians, although patients also completed diary cards for quality of life measurement. The commonest predominant symptom being chest pain is usually assessed using VAS from 1 to 10. Also, few symptoms like hemoptysis may be intermittent and respond variably to palliative radiotherapy, further making it difficult to evaluate the response. As a result, optimal dose and fractionation to relieve these symptoms and to achieve durable response remains debatable.
Various patient and tumor related factors help in deciding about optimal radiotherapy schedules for palliation. Age, performance status, presence of extrathoracic disease, predominant thoracic symptoms and expected survival of patients can guide in this aspect. The results from the MRC trials are of particular interest. MRC 91 and 96 trials had randomized patients with locally advanced nonsmall cell lung cancer (NSCLC) to receive fractionated RT versus once weekly regimen of 17 Gy in 2 fractions for palliation of thoracic symptoms., Both of these studies included patients irrespective of PS and without extrathoracic disease. Their first trial compared 30 Gy given in 10 fractions with 17 Gy given in 2 fractions. Both arms had similar rates and durations of symptom palliation. Cough was palliated for 65% of patients, hemoptysis for 81% and chest pain for 75% patients. In MRC 96 study, the symptom relief was rapid with short course RT whereas it was prolonged with fractionated RT, along with small but significant survival advantage with fractionated course of RT. So the authors recommended prolonged RT for those with better PS and expected longer survival. Another MRC 92 study, which selectively studied patients with advanced NSCLC disease and poor PS, randomized to 17 Gy/2# versus 10 Gy single fraction and assessed response in terms of symptom relief. Both arms had similar response rates, however, side effects like dysphagia and myelopathy were reported to be more common in 17 Gy/2# arm.
Literature reports variable response to different RT regimens depending upon the predominant symptom. Results of a study addressing two fractions of 8.5 Gy given 1 week apart for 48 patients with good/poor PS and advanced NSCLC suggested that greatest palliation rates were demonstrated for hemoptysis and cough. Relief of cough to TRT has been reported to range from 20% to 80%, with 10 Gy single fraction being better regimen in terms of cough relief in study carried out at our center, with 87.5% patients having relief. In the current study, extent of relief in symptoms of chest pain versus other symptoms was not significantly different (P = 0.867). Relief from other symptoms like chest pain and hemoptysis ranges from 40–80% to 60–100% respectively, in various studies, with protracted regimens being better.,, The rates of palliation for chest pain, cough, and dyspnea reported here are similar to those of other trials that used similar or more protracted treatment regimens that is, overall 80% response rates to radiation with more than half of patients having more than 50% relief in symptoms., There was a trend toward better symptom relief with daily course of RT. However, the number of patients receiving daily course was very small (n = 21).
Nestle et al. conducted a randomized study in patients with inoperable NSCLC patients, comparing TRT 32 Gy/16 fractions to 60 Gy/30# and assessed symptom relief and local control radiologically. He reported that the local control and progression free survival as well as symptom relief was similar in both arms, suggesting no advantage of 6 weeks RT over shorter regimens. However, on the contrary, there are few trials that report better survival with fractionated RT over a short course., Senkus-Konefka et al. randomized 100 patients of NSCLC not suitable for radical treatment with significant thoracic symptoms into 20 Gy/5# and 17 Gy/2# and assessed for symptom control and OS. He reported similar symptom relief but better median survival in short course arm (8 months vs. 5.3 months, P = 0.016). But this trial results had to be interpreted cautiously due to a smaller number of patients. In the current study, most of the patient received short course TRT, and they tolerated it well with the majority of patients having symptom relief of >50% in all the symptoms. The median duration of symptom relief and OS were not significantly different between the two different regimens of radiotherapy. The reported median survival in our study of 5 months is similar to MRC 92 study wherein median survival was 4 months and reflected on the poor performance patients that were included in the study.
The results of a randomized study from our institute, supported by International Atomic Energy Agency, comparing 20 Gy/5#, 17 Gy/2# and 10 Gy single fraction reported that there was no difference in terms of relief, acute toxicities and survival at 1 year between the various fraction regimens. However, younger patients <60 years had better survival at 1 year. Similarly in the current study also, the patients <60 years age had significantly better OS as compared to older counterparts. A possible reason could be that younger patients were more likely to receive and tolerate chemotherapy resulting in improved survival. There have been very few studies reporting role of palliative TRT for small cell lung cancer (SCLC). In the current study, SCLC patients seemed to have better symptom relief with palliative TRT, although not statistically significant.
Shorter hypofractionated schedules not only require fewer trips to the RT facility but as patients receiving weekly fractionation were treated on Saturdays, thereby sparing the possible machine space and resources for the treatment of curative patients on weekdays in a high volume center. A clear advantage of the very short hypofractionated regimen is that it enables patients with short expected survival time to spend more of their remaining time away from the hospital. In the recently published cochrane review on palliative RT for lung cancer, authors have concluded that a short course thoracic palliative RT can be used for the majority of patients with locally advanced NSCLC having thoracic symptoms and low PS. It is a good treatment option, especially in resource constrained countries.
| » Conclusion|| |
Overall, both the schedules of thoracic radiation delivered over a week are effective and pragmatic. With short expected life span, these short course fractionation schedules are a convenient option for palliation of thoracic symptoms, resulting in fewer visits to hospital as well as reducing the stay away from home along with educing economic burden on the families. Shorter course regimens have the advantage of sparing resources in high volume centers and simultaneously providing a similar benefit with regard to palliation and survival compared to protracted regimens.
| » Acknowledgments|| |
We would like to acknowledge the support of Sr. Rupali Bhide /Mr. Jitendra Arora for assisting in clinic.
| » References|| |
Okawara G, Mackay JA, Evans WK, Ung YC, Lung Cancer Disease Site Group of Cancer Care Ontario's Program in Evidence-based Care. Management of unresected stage III non-small cell lung cancer: A systematic review. J Thorac Oncol 2006;1:377-93.
Brundage MD, Bezjak A, Dixon P, Grimard L, Larochelle M, Warde P, et al.
The role of palliative thoracic radiotherapy in non-small cell lung cancer. Can J Oncol 1996;6 Suppl 1:25-32.
Sirzén F, Kjellén E, Sörenson S, Cavallin-Ståhl E. A systematic overview of radiation therapy effects in non-small cell lung cancer. Acta Oncol 2003;42:493-515.
Langendijk JA, ten Velde GP, Aaronson NK, de Jong JM, Muller MJ, Wouters EF. Quality of life after palliative radiotherapy in non-small cell lung cancer: A prospective study. Int J Radiat Oncol Biol Phys 2000;47:149-55.
Numico G, Russi E, Merlano M. Best supportive care in non-small cell lung cancer: Is there a role for radiotherapy and chemotherapy? Lung Cancer 2001;32:213-26.
Lutz ST, Huang DT, Ferguson CL, Kavanagh BD, Tercilla OF, Lu J. A retrospective quality of life analysis using the Lung Cancer Symptom Scale in patients treated with palliative radiotherapy for advanced nonsmall cell lung cancer. Int J Radiat Oncol Biol Phys 1997;37:117-22.
A Medical Research Council (MRC) randomised trial of palliative radiotherapy with two fractions or a single fraction in patients with inoperable non-small-cell lung cancer (NSCLC) and poor performance status. Medical Research Council Lung Cancer Working Party. Br J Cancer 1992;65:934-41.
Macbeth FR, Bolger JJ, Hopwood P, Bleehen NM, Cartmell J, Girling DJ, et al.
Randomized trial of palliative two-fraction versus more intensive 13-fraction radiotherapy for patients with inoperable non-small cell lung cancer and good performance status. Medical Research Council Lung Cancer Working Party. Clin Oncol (R Coll Radiol) 1996;8:167-75.
Sundstrøm S, Bremnes R, Aasebø U, Aamdal S, Hatlevoll R, Brunsvig P, et al.
Hypofractionated palliative radiotherapy (17 Gy per two fractions) in advanced non-small-cell lung carcinoma is comparable to standard fractionation for symptom control and survival: A national phase III trial. J Clin Oncol 2004;22:801-10.
Gehdoo RP. Cancer pain management. Indian J Anaesth 2006;50:375-90. [Full text]
Medical Research Council Lung Cancer Working Party. Inoperable non-small cell lung cancer (NSCLC): A medical research council trial of palliative radiotherapy with two fractions or ten fractions. Report to the Medical Research Council by its Lung Cancer Working Party. Br J Cancer 1991;63:265-70.
Plataniotis GA, Kouvaris JR, Dardoufas C, Kouloulias V, Theofanopoulou MA, Vlahos L. A short radiotherapy course for locally advanced non-small cell lung cancer (NSCLC): Effective palliation and patients' convenience. Lung Cancer 2002;35:203-7.
Sharma V, Sanghavi V, Agarwal JP, Deshpande R, Levin CV, Rosenblatt E, et al
. Single institution prospective randomized trial of radiation as a sole modality in palliation of advanced non-small cell lung cancer-an International Atomic Energy Agency study. Open Access Sci Rep 2012;1:1-8.
Simpson JR, Francis ME, Perez-Tamayo R, Marks RD, Rao DV. Palliative radiotherapy for inoperable carcinoma of the lung: Final report of a RTOG multi-institutional trial. Int J Radiat Oncol Biol Phys 1985;11:751-8.
Vyas RK, Suryanarayana U, Dixit S, Singhal S, Bhavsar DC, Neema JP, et al.
Inoperable non-small cell lung cancer: Palliative radiotherapy with two weekly fractions. Indian J Chest Dis Allied Sci 1998;40:171-4.
Nestle U, Nieder C, Walter K, Abel U, Ukena D, Sybrecht GW, et al.
Apalliative accelerated irradiation regimen for advanced non-small-cell lung cancer vs. conventionally fractionated 60 GY: Results of a randomized equivalence study. Int J Radiat Oncol Biol Phys 2000;48:95-103.
Bezjak A, Dixon P, Brundage M, Tu D, Palmer MJ, Blood P, et al.
Randomized phase III trial of single versus fractionated thoracic radiation in the palliation of patients with lung cancer (NCIC CTG SC.15). Int J Radiat Oncol Biol Phys 2002;54:719-28.
Kramer GW, Wanders SL, Noordijk EM, Vonk EJ, van Houwelingen HC, van den Hout WB, et al.
Results of the Dutch National study of the palliative effect of irradiation using two different treatment schemes for non-small-cell lung cancer. J Clin Oncol 2005;23:2962-70.
Senkus-Konefka E, Dziadziuszko R, Bednaruk-Mlynski E, Pliszka A, Kubrak J, Lewandowska A, et al.
Aprospective, randomised study to compare two palliative radiotherapy schedules for non-small-cell lung cancer (NSCLC). Br J Cancer 2005;92:1038-45.
Lester JF, Macbeth F, Toy E, Coles B. Palliative radiotherapy regimens for non-small cell lung cancer. Cochrane database Syst Rev 2006. Oct 18;(4):CD002143.
[Table 1], [Table 2], [Table 3]