Abhishek Puri

Comparison between weekly cisplatin‐enhanced radiotherapy and cetuximab‐enhanced radiotherapy in locally advanced head and neck cancer: First retrospective study in Asian population

To present a direct comparison between chemotherapy‐enhanced radiotherapy (CERT) and biotherapy‐enhanced radiotherapy (BERT) in locally advanced head and neck cancer.

Cervical Neck Dissection for Complete Responders in Head-and-Neck: A Utilitarian Ideal? In regard to Thariat et al “Prediction of Neck Dissection Requirement After Definitive Radiotherapy for Head-and-Neck Squamous Cell Carcinoma.” (Int J Radiat Oncol Biol Phys 2012;82:e367–e374)

To the Editor: Thariat et al (1) have validated their institutional preference by predicting low rates of locoregional recurrence in completely responding N2-N3 cervical neck nodes but it does not include distant metastases. Current methods to screen for distant metastases in locally advanced head-and-neck primary tumors, at initial presentation, grossly underestimate its true extent of spread (2). This explains why locoregional neck nodes are a key determinant of the prognosis and ultimate outcome (3). Retrospective data are prone to heterogeneity and bias; with this caveat, the current recommendations gleaned from meta-analyses have failed to show statistically significant survival outcomes for comprehensive neck dissection (4). Neck nodes, scored as completely responding, clinically or radiologically, after definitive chemoradiotherapy corresponds only to 3 log cell kill (5). Residual micrometastatic disease, not evident by current pathologic examination, tends to fail only distantly (6). Presumably, it is because of altered tumor host interaction at neck nodal region forcing tumor cells to migrate out of their niche, which is clinically evident as low rates of regional recurrence. Contrary to conventional reasoning (7), neck dissection does reduce the distant metastasis rate, affecting overall survival (8). In patients with associated human papillomavirus infection, locally advanced T stage (indirectly seeding the regional neck nodes) alone is a significant factor on multivariate analysis (9). The salvage rates for recurrent disease and delayed metastases (often as multiple neck nodes and contralateral disease) is very poor (10). Common weal is a utilitarian ideal; it is expected that sufficient restraint should be exercised in advocating observation alone for patients with a complete response in the neck, especially for N2-N3 nodes in head-and-neck primary cancer cases after definitive treatment. Observation alone vs upfront neck dissection in complete responders for N2-N3 neck nodes is a vexing question that can only be addressed by a prospective phase III randomized trial with

Correlation of six-minute walk test, pulmonary function test and radiation pneumonitis in the management of carcinoma of oesophagus: A prospective pilot study

Purpose: To correlate six-minute walk test (6MWT) and pulmonary function test (PFT) with incidence of radiation pneumonitis (RP) while treating patients with oesophageal cancer with conformal radiotherapy. Methods: Forty-five patients were selected to the study protocol. Pulmonary evaluation was done objectively by chest x-ray (CXR), 6MWT and PFT and subjectively by symptoms of cough, dyspnoea and fatigue. These tests were performed before radiation and then repeated at 1, 3, 6 and 9 months after treatment. The dose-volume histogram (DVH) was used to derive doses received by lung and organs at risk. χ 2 -test was used for calculating the p value. Results: The walk distance change (WDC) correlated with the changes in PFT values ( p = 0.001) were done at 3 and 9 months after radiation, respectively. V30 values of ≥20% correlated with the incidence of acute pneumonitis ( p = 0.007). 6MVT/vital capacity (VC) values of ≤4 ft/l had a correlation with the incidence of clinically symptomatic RP at 9 months. Conclusion: 6MWT and PFT are supplementary to each other for assessing the lung function status; but their individual role in predicting RP is weak. However, they are complementary to each other in assessing the risk of radiation-induced lung dysfunction.

In Regard to Schlocker and Corn

hazardous sulfur and chlorine compounds. To date, there is a large body of evidence that chronic exposure to these compounds significantly increases the risk of occupational lymphomas (7-9). Besides, the bad working conditions and the emergence of numerous diseases were at the origin of the first strikes and trade unions in the silk industry. One of the most famous characters of this period was a women, Lucie Baud, a trade unionist who was a contemporary of Despeignes and Colliat (6, 10). Hence, in addition to the possible microbial origin, a chemical origin may also be evoked for explaining the tumor of the Despeignes’s patient. Besides, these two hypotheses are not exclusive. The first tumor treated by X rays could also have been occupational. As mentioned in the letter, a microbial origin can also be evoked to explain the gastric ulcer of Despeignes. Despeignes, as Director of Hygiene for the city of Chambery for 30 years, may have manipulated hazardous chemicals as well. However, intense analyses of infected samples and micro-organism cultures were more likely responsible for the disease of Despeignes. I thank the author for the citation of Shakespeare at the end of his letter: it is really appropriate! However, the words that come immediately after the citation in The Tempest also fit our case and give us some responsibilities to better consider the works of the pioneers: “., what to come, In yours and my discharge.”

Validation of a software upgrade in a monte carlo treatment planning system by comparison of plans in different versions

Purpose: Validation of a new software version of a Monte Carlo treatment planning system through comparing plans generated by two software versions in volumetric-modulated arc therapy (VMAT) for lung cancer. Materials and Methods: Three patients who were treated with 60 Gy/30 fractions in Elekta Synergy™ linear accelerator by VMAT technique with 2% statistical uncertainty (SU) were chosen for the study. Multiple VMAT plans were generated using two different software versions of Monaco treatment planning system TPS (V5.10.02 and V5.11). By keeping all other parameters constant, originally accepted plans were recalculated for the SUs of 0.5%, 1%, 2%, 3%, 4%, and 5%. For plan evaluation, the metrics compared were conformity Index (CI), homogeneity Index (HI), dose coverage to planning target volume (PTV), organ at risk (OAR) doses to spinal cord, pericardium, bilateral lungs-PTV, esophagus, liver, normal tissue integral dose (NTID), volumes receiving dose >5 and >10 Gy, calculation time (tCT), and gamma pass rates. Results: In both versions, CI and HI improved as the SU increased from 0.5% to 5%. No significant dose difference was observed in Dmean to PTV, bilateral lungs-PTV, pericardium, esophagus, liver, normal tissue volume receiving >5, and >10 Gy and NTID. It was observed that while the tCT and gamma pass rates decreased, the maximum dose to PTV increased as the SU increased. No other significant dose differences were observed between the two MC versions compared. Conclusion: For lung VMAT plans, in both versions, SU could be accepted up to 3% per plan with reduced tCT without compromising plan quality and deliverability by accepting variations in point dose and an inhomogeneous dose within the target. The plan quality of Monaco™V5.10.02 was similar to Monaco™TPS-V5.11 except for tCT.

Is Elective Irradiation to the Lower Neck Necessary for N0 Nasopharyngeal Carcinoma?: In Regard to Macmillan MS et al. (Int J Radiat Oncol Biol Phys 2010;77:1397–1402)

To the Editor: Gao et al. (1) summarized their experience with exclusive Grade III nasopharyngeal carcinoma and suggest the possibility of field reduction based on their results. I feel that it is pepperedwith generalizations and the results need to be interpreted with caution. Grade III nasopharyngeal carcinoma, also called as Regaud-Schmincke tumor (2) (entire cohort in their study), represents a distinct entity that is highly sensitive to both chemotherapy and radiotherapy with high response rates for locoregional interventions but is aggressive systemically (3). Retrospective studies have documented a trend toward a distinct clinical behavior (and patterns of failure) in Asian populations (4). Magnetic resonance imaging (MRI) impacts significantly on the T stage, and, in one study, was associated with nearly 40% of clinical stage migration (5). Upstaging patients selects them for more aggressive therapeutic approaches and is absolutely essential for accurate delineation of gross tumor volume. Conversely, downstaging would have spared them from such a therapeutic strategy. The authors have failed to use this modality in staging and is more surprising because T stage as a prognostic factor (1) (as in other studies) has impacted the overall survival of their patient cohort. Platinum-based chemotherapy (or in combination) has shown 50–78% overall response rates and 13–39% complete response rates (3). However, current consensus guidelines (6) stress concurrent chemoradiation for any T stage over T1 irrespective of nodal status or histology. A high proportion of the patients in given study received neo-adjuvant chemotherapy with concurrent regimes reserved only for a minority of advanced T lesions. Lack of protocol and physician discretion alone is a serious omission. The authors’ results for local and excellent nodal control rates are in consonance with the published results (3); interestingly, only 4 documented patients experienced neck recurrence. However, it is not clear about the preexisting T stage of patients those who failed given the heterogeneous distribution of patients with variable T stage at presentation. Given the close proximity of low neck nodes to regions that received radiation, is it possible that these were ‘‘incidentally irradiated’’ with chosen bilateral fields? The principle of primum succurrere should guide us for rational field designs and management; not at the cost of retrospective generalizations and distinct biological entities, which do not form the bulk of clinical presentation in nonendemic parts of the world.

Nonstandard protocol for treatment of carcinoma esophagus does not suffice for identification of prognostic markers in retrospective study.

To the Editor: We read with interest the article by Ishihara et al. (1). There are several methodologic flaws in the write-up that raise some queries and perhaps do not justify the inclusion of the article in the journal. The INT 0123 trial (Radiation Therapy Oncology Group 94-05) for concurrent chemoradiation reduced the treatment margins by 5 cm proximal and distal to the identified esophageal carcinoma treated to a dose of 50.4 Gy in 28 fractions and established the standard of care for margins (2). Surprisingly, only margins for Stage I cancer have been defined, and for the remaining stages, ‘‘similar’’ margins have been quoted. The authors have not justified the use of reduced margins at their institution by any means. Use of split-course radiation therapy is not warranted, and that subset of patients has also been included in the final analysis. After the INT 0123 trial was published in 2002, it is surprising that the authors persisted with a dose of 60 Gy given concurrently with chemotherapy when the standard of care had shifted to 50.4 Gy delivered in 28 fractions. The role of surgery after definitive chemoradiation as the standard of care has been addressed by several randomized trials (3, 4), although opponents of surgery argue that none of the studies had a definitive chemoradiation arm. Although a nonoperative approach after definitive chemoradiation avoids esophagectomy in selected patients, this is associated with a high rate of locally recurrent or persistent disease (5). Regarding esophagectomy in potentially resectable patients, those with a less than complete response with clear margins reportedly had a 35% 5year overall survival rate (6). The only curative-intent treatment modality for locoregional relapse is salvage surgery (7). Unfortunately, the authors have advocated the use of photodynamic therapy without resorting to surgery; this approach is more galling because the study population had a good performance status. Furthermore, there has been no randomized trial to compare the photodynamic therapy upfront with the current standard of care, that is, esophagectomy after chemoradiation. We believe that this is less than adequate treatment and needs to deplored. Retrospective analyses are as such limited in their clinical outlook in terms of heterogeneity and low statistical power. To top that, the present retrospective study does not indicate a standard treatment protocol being practiced for squamous esophageal cancer. To deduce meaningful conclusions from such a protocol would be ruinous in terms of prognostication.