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| LETTER TO THE EDITOR |
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| Year : 2021 | Volume
: 4
| Issue : 4 | Page : 775-777 |
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Authors' reply to Nanda et al. and Mathew
Tapas Kumar Dora1, Jayashree Deshmukh1, Abhishek Chatterjee2
1 Department of Radiation Oncology, Homi Bhabha Cancer Hospital, Sangrur, Pubjab, India
2 Tata Memorial Centre, Mumbai, Maharashtra, India
| Date of Submission | 10-Nov-2021 |
| Date of Decision | 17-Nov-2021 |
| Date of Acceptance | 19-Nov-2021 |
| Date of Web Publication | 29-Dec-2021 |
Correspondence Address:
Tapas Kumar Dora
Department of Radiation Oncology, Homi Bhabha Cancer Hospital, Civil Hospital Campus, Sangrur - 148 001, Punjab
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/crst.crst_277_21
How to cite this article:
Dora TK, Deshmukh J, Chatterjee A. Authors' reply to Nanda et al. and Mathew. Cancer Res Stat Treat 2021;4:775-7 |
Nanda et al. have correctly highlighted the debate regarding whether the dosimetric advantage of volumetric modulated arc therapy (VMAT) over three-dimensional-conformal radiotherapy (3D-CRT) reflects in clinically significant benefits, particularly in reduced lung and heart toxicities.[1] However, in the absence of VMAT, 3D-CRT can be a good treatment modality for low-resource setups at a lesser treatment cost. In our study,[2] positron emission tomography-computed tomography (PET-CT) was not performed routinely in all cases, because of the lack of PET facility at our center. However, a PET scan was recommended whenever normal CT scanning revealed suspicious findings.
The variation in dose prescription was based on the tumor location and was not a limitation of the RT technique (VMAT or 3D-CRT). Although we aimed for dose escalation beyond 60 Gy, in case of lower-third and gastroesophageal junction tumors where the planning target volume (PTV) went further below the stomach, the dose was limited to 59.4 Gy in case of squamous cell carcinomas and 54 Gy in case of adenocarcinomas. In case of long-segment disease, where after PTV generation, the entire esophagus was going to be radiated, we limited the dose to 50.4 Gy. In other words, we limited the dose to 54 Gy or 50.4 Gy only when we were really unable to use a dose of up to 63 Gy. We agree that the boost PTV was 1–2 cm less than the initial PTV in both the superior and inferior margins. Shielding was used in cobalt settings using the blocks provided along with the Babatron-II machine to reduce the lung doses.
We really appreciate the suggestion to perform a subgroup analysis of the cardiac doses based on the location of the primary tumor. Therefore, we grouped the disease into three categories: A-cervical plus upper-third, B-upper-third plus middle-third, C-middle-third plus lower-third. This was because even though the epicenter was in the lower-third or upper-third, after leaving a margin of 3–4 cm on either side, mostly the PTV encroached onto the middle-third part. One-way analysis of variance to compare the means showed a statistically significant difference (P < 0.05) between all groups (A vs. B, B vs. C, and C vs. A) for all the cardiac parameters (mean, V25, V30, V35, V40, V45).
Grade 2/3 pharyngo-esophagitis was seen in 32.8% versus 19.6% in VMAT versus conformal technique, which was similar to the incidence with cisplatin plus 5-fluorouracil (5-FU) based chemotherapy (25.6%) as reported in a meta-analysis[3] and cisplatin alone (38.5%) as reported in a randomized controlled trial.[4] However, the INT 0123 study[5] showed higher grade 2 (19%) and grade 3 (46%) toxicities, not limited to esophagitis in the arm receiving 64.8 Gy dose of radiation. A multicenter, retrospective study[6] comparing cisplatin plus 5-FU (Arm A) with carboplatin plus paclitaxel (Arm B) has shown a higher treatment completion rate (82% vs. 57%, P = 0.010) in Arm B with fewer nonhematologic adverse events (18% vs. 38%, P = 0.028) but comparable outcomes in terms of disease-free survival and overall survival. A retrospective study from the Tata Memorial Hospital, Mumbai,[7] has shown similar rates of Grade 2 and 3 pharyngoesophageal mucositis (35.2% and 2.8%, respectively), with carboplatin plus paclitaxel and estimated 1-, 2-, and 3-year survival rates of 70%, 47%, and 39%, respectively. The CROSS study with paclitaxel and carboplatin in combination with neoadjuvant radiation also showed that Grade 3 or higher nonhematologic toxicities occurred in only 11% of the patients.
We also acknowledge the concerns raised by Dr. Mathew.[8] In our study as well, malnutrition posed a challenge to successful chemoradiation in the majority of patients, especially in those from rural areas and those with lower educational and financial status. To maintain the nutritional rehabilitation, we ensured the placement of endoscopically-guided Ryle's tube before starting chemoradiation in most of the cases. For this study, we obtained a list of all patients with esophageal cancer treated with radical intent from the “Radiation Oncology Information System” software based-database and included those who had completed the planned treatment schedule in the final analysis. We agree that it would have been beneficial if we had recorded the baseline body mass index of the patients, but the height and weight details were not available in the electronic medical records, as they mostly comprised chemotherapy charts attached to patient files (which were actually returned to the patients). As was rightly pointed out by Dr. Mathew, toxicity with respect to the lung and heart was definitely expected to be reported in our study, but unfortunately the toxicity records were unavailable for the majority of the patients. We also agree that it is difficult to comment on the overall survival benefit with concurrent chemotherapy without conducting proper randomized studies. The short follow-up duration in our retrospective audit with a small sample size was a major weakness of our study. We were also surprised to see a similar comparable intermediate to low lung dose between patients treated with VMAT and 3D-CRT, but all credit for this goes to the physicists behind the plans. We agree that it is time to critically look at dose escalation in esophageal squamous cell carcinoma. However, we also wonder why it behaves differently from head and neck malignancies in terms of dose escalation; possibly biomarkers could answer this. Proton beam therapy will definitely help in further reducing low-dose spillage to lung volumes significantly as compared to VMAT. However, if this improvement does not result in a decrease in clinical pneumonitis, the cost of proton therapy would need to be considered for treating a disease with such poor outcomes, i.e., a 2-year OS of 36%–40%.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | |  |
| 1. | Nanda SS, Mukherji A, Pradhan S. Precision radiotherapy in carcinoma esophagus: Does conformity translate into significant clinical outcomes? Cancer Res Stat Treat 2021;4:773-4.  [Full text] |
| 2. | Dora TK, Deshmukh J, Chatterjee A, Goel A, Bose S, Singh A, et al. Conformal radiation therapy versus volumetric arc therapy in high dose concurrent chemoradiotherapy for carcinoma esophagus: A retrospective analysis. Cancer Res Stat Treat 2021;4:456-65. [Full text] |
| 3. | Zhu LL, Yuan L, Wang H, Ye L, Yao GY, Liu C, et al. A meta-analysis of concurrent chemoradiotherapy for advanced esophageal cancer. PLoS One 2015;10:e0128616. |
| 4. | Kumar S, Dimri K, Khurana R, Rastogi N, Das KJ, Lal P. A randomised trial of radiotherapy compared with cisplatin chemo-radiotherapy in patients with unresectable squamous cell cancer of the esophagus. Radiother Oncol 2007;83:139-47. |
| 5. | Minsky BD, Pajak TF, Ginsberg RJ, Pisansky TM, Martenson J, Komaki R, et al. INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: High-dose versus standard-dose radiation therapy. J Clin Oncol 2002;20:1167-74. |
| 6. | Honing J, Smit JK, Muijs CT, Burgerhof JG, de Groot JW, Paardekooper G, et al. A comparison of carboplatin and paclitaxel with cisplatinum and 5-fluorouracil in definitive chemoradiation in esophageal cancer patients. Ann Oncol 2014;25:638-43. |
| 7. | Noronha V, Prabhash K, Joshi A, Patil VM, Talole S, Nakti D, et al. Clinical outcome in definitive concurrent chemoradiation with weekly paclitaxel and carboplatin for locally advanced esophageal and junctional cancer. Oncol Res 2016;23:183-95. |
| 8. | Mathew AS. Transitioning from 3DCRT to volumetric modulated arc therapy: Is more really better? Cancer Res Stat Treat 2021;4:774-5. [Full text] |
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