Pragya Shukla

Circadian variation in radiation-induced intestinal mucositis in patients with cervical carcinoma†

Mucositis, a radiotherapy‐associated toxicity, is an important factor determining morbidity and treatment compliance. Gastrointestinal mucositis in patients undergoing radiotherapy may also depend on time of administration of radiation in addition to several other factors. The presence of any correlation between the severity of acute gastrointestinal mucositis in cervical carcinoma patients and the time of irradiation was prospectively evaluated.

Interaction of drug metabolizing cytochrome P450 2D6 poor metabolizers with cytochrome P450 2C9 and 2C19 genotypes modify the susceptibility to head and neck cancer and treatment response.

The present case-control study attempted to investigate the association of poor metabolizer (PM) genotypes of cytochrome P450 2D6 (CYP2D6*4 and CYP2D6*10) with squamous cell carcinoma of head and neck (HNSCC) and treatment response in patients receiving chemotherapy or combination of chemo- and radiotherapy. Cases with the PM genotypes of CYP2D6 displayed a significantly increased risk for HNSCC as compared to wild type genotypes. The risk was found to further increase in cases (up to 4.8) carrying combination of PM genotypes of CYP2D6, CYP2C9 (CYP2C9*2) or CYP2C19 (CYP2C19*2), suggesting that synergism amongst the PM genotypes of drug metabolizing CYPs leads to impairment in the detoxification of the tobacco carcinogens. A small increase in the risk in tobacco (chewers or smokers) or alcohol users in cases with CYP2D6*4 allele while no change or even a small decrease in risk in cases with CYP2D6*10 allele when compared to non-tobacco or alcohol users have suggested that CYP2D6 genotypes alone do not appear to interact significantly with environmental risk factors in modifying the susceptibility to HNSCC. Furthermore, most of the cases carrying PM genotypes of CYP2D6 did not respond to the treatment. Moreover, higher prevalence of non-responders among cases carrying combination of CYP2D6*4 or CYP2D6*4, CYP2C9*2 and CYP2C19*2 have demonstrated that interaction of PM genotypes may not only significantly modify the susceptibility to HNSCC but also the treatment response.

Oral mucositis in morning vs. evening irradiated patients: a randomised prospective study.

Purpose: Patients of head and neck cancer undergoing radiotherapy develop oral mucositis. The severity of mucositis may also depend on the time of administration of radiation apart from patient-related factors. The most radiosensitive phase of the cell cycle (G2-M) occurs in the late afternoon and evening in human oral mucosa; therefore, it is more vulnerable to radiation injury in the evening. The present study evaluated prospectively the severity of acute oral mucositis in head and neck carcinoma patients irradiated in the morning (08:00–11:00 h) versus late afternoon/evening (15:00–18:00 h). Method: A total of 212 patients of head and neck carcinoma were randomised to morning (08:00–11:00 h) and evening (15:00–18:00 h) groups. The grades of oral mucosa ulceration were compared in the two groups. Results: The grades of mucositis were marginally higher in the evening-irradiated group than in the morning-irradiated group 38% vs. 26% (p = 0.08). Conclusion: The observed incidence of grade III/IV mucositis in morning vs. evening irradiated patients may be because of the existence of circadian rhythm in the cell cycle of normal mucosa. This knowledge may provide a possibility of treating the patients with decreased toxicity to oral mucosa.

Metastatic squamous cell carcinoma neck with occult primary: A retrospective analysis

Introduction: Metastatic carcinoma in the lymph nodes of the neck from an unknown primary is relatively rare, accounting for about 3% of all head and neck cancers. Management of secondary neck of undetermined primary is controversial. Materials and Methods: The case records of all the patients treated in the Department of Radiotherapy, Chatrapati Shahuji Maharaj Medical University, from Oct 1999 to Sep 2004, were studied and the patients with secondary neck without a known primary tumor were analyzed in detail to elucidate the outcome of various treatment modalities in various stages of the disease. One hundred and forty patients were found to be eligible for this analysis. Initial treatment could be divided into two categories: concurrent chemoradiation (n=76) and radiotherapy alone (n=64). Results: The patients who had received radiotherapy alone (53.1%) had lesser complete response as compared to those who had received chemoradiotherapy (68.4%). The overall survival duration in patients of the radiotherapy treatment group ranged from 5 to 60 months, with an average (±SD) of 31.06 ± 21.01 months, while in the chemoradiotherapy treatment group it ranged from 6 to 60 months, with an average (±SD) of 39.42 ± 21.33 months. Both hematological and nonhematological toxicities, although higher in the chemoradiotherapy group, showed statistically insignificant differences. Conclusion: To the best of our knowledge, this is the only study evaluating the role of concurrent chemoradiation in cases of secondary neck with primary unknown. The improved response rates along with an increased survival (both disease free and overall) show the superiority of chemoradiotherapy in the management of such cases.

Quantification of coronary artery motion and internal risk volume from ECG gated radiotherapy planning scans

BACKGROUND Radiotherapy for carcinoma of breast and thoracic structures involves inadvertent radiation to heart and coronary arteries (CA). Coronary artery stenosis in high radiation dose segments has been documented. Cardiac and respiratory motion induced displacement of CA and internal risk volume (IRV) margin remains inadequately quantified. MATERIAL AND METHODS Twenty cases of carcinoma breast, lung and lung metastasis were enrolled in this study. ECG gated intravenous contrast enhanced computed tomography (CECT) scans were performed in inspiratory breath hold (IBH) and expiratory breath hold (EBH). The images were segregated into inspiratory systole (IS), inspiratory diastole (ID), expiratory systole (ES) and expiratory diastole (ED) sets. Left anterior descending (LAD), limited segment of LAD close to chest wall (short LAD), right coronary artery (RCA), Left circumflex artery (LCX) and left ventricle (LV) were delineated in all four sets. Mean displacements in systole versus diastole and inspiration versus expiration were calculated in three co-ordinates [anterio-posterior (Z), left-right (X) and cranio-caudal (Y)]. RESULTS Mean of displacement (mm) between systole and diastole (IS versus ID; and ES versus ED) in X, Y, Z co-ordinates were: LAD 3.0(±1.6), 2.8(±1.5), 3.6(±2.0); Short-LAD 3.0(±1.1), 0.8(±0.4), 2.4(±0.6); LV 2.4(±1.6), 1.7(±1), 5.0(±1.5); LCX 4.9(±1.6), 2.9(±1.3), 5.1(±1.9); RCA 6.6(±2.2), 3.6(±2.1), 5.9(±2.2). Mean displacement between inspiration and expiration (IS versus ES; and ID versus ED) in X, Y, Z axes were: LAD 3.3(±1.5), 8.0(±3.4), 3.8(±1.8); Short-LAD 2.7(±1), 12.2(±4.4), 3.3(±1.5); LV 2.9(±1.4), 9.8(±3.3), 4.7(±1.9); LCX 2.9(±.8), 9.7(±3.2), 6.2(±2.5); RCA 2.6(±1.3), 7.6(±2.5), 3.8(±1.7). CONCLUSION Radial (RM), cranio-caudal margin (CC) of 7mm, 4mm in breath-hold radiotherapy whereas RM, CC of 7mm, 13mm respectively in free breath radiotherapy will cover the range of motions of CA, LV and can be recommended as IRV for these structures.

A prospective comparision of sequential chemoradiation vs concurrent chemoradiation in locally advanced oropharyngeal carcinomas

Purpose: Induction chemotherapy has shown to provide consistent benefit for local control in primary treatment of advanced oropharyngeal cancer. The beneficial role of chemoradiation following induction chemotherapy over concurrent chemoradiation has not been evaluated. Present study evaluates the same prospectively. Method: Out of 135 patients of locally advanced oropharyngeal carcinoma, 105 patients were found eligible and randomized to treat either with induction chemotherapy consisting of 2-3 cycles of cisplatin and 5- Florouracil followed by low dose weekly cisplatin based chemoradiotherapy (treatment arm: n=48) or chemoradiotherapy only (control arm: n=57). The primary tumor and regional lymph drainage areas received 66-70 Gy in 6.5 to 7 weeks by fractionated dose schedule. Results: The response rate and acute toxicity (primary end points) in both the arms were found to be similar (P>0.05) The points disease free survival and overall survival (secondary end points) were significantly (P

Cardioprotective radiotherapy: The circadian way

Radiotherapy (RT) has been established to improve both local control as well as overall survival rates in breast cancer. However, RT especially in left-sided breast cancer also irradiates a portion of the heart. Radiation associated toxicity to the heart assumes significance because of improval in survival of breast cancer patients. A circadian pattern has been reported in the myocardial oxygen demand and myocardial ischaemia with the cardiac tissue being more susceptible to injury between 6 am and noon. Radiation damages blood vessels of all sizes causing an increase in capillary wall permeability and dilatation of vessels leading to the characteristic radiation erythema followed by an inflammatory cell infiltrate. Coronary artery spasm may be the reason behind some cases of sudden death occurring in patients after radiation therapy. Endothelial behaviour also has a circadian variation and vasodilation is significantly attenuated in the morning. Critical coronary artery disease occurs 10-15 years after radiotherapy. Radiation in the morning hours may be one of the associated risk factor. The application of chrono-therapeutics with radiation therapy in carcinoma breast and in other chest wall irradiation, could possibly decrease the radiation associated cardiac toxicity.

Deep vein and artery thrombosis associated with cetuximab-based chemoradiotherapy

Molecular targeted agents have lower hematological toxicity. However, specific side-effects such as allergic rashes, skin reactions and high cost limit their use. We report a case of 35-year-old male patient with carcinoma of left tonsil treated with concurrent cetuximab and radiotherapy. After four weeks of treatment, the patient developed sudden onset of pain in the left calf region radiating to the left foot. Doppler study of the left lower limb revealed complete thrombosis of superficial femoral, popliteal and proximal tibial arteries and veins and no flow in anterior tibial artery and lower posterior tibial artery. Emergency embolectomy was done. After 48 h of observation, no improvement was noted. A repeat Doppler examination showed similar finding. Ultimately a left lower limb amputation was done. We report simultaneous arterio-venous thrombosis associated with cetuximab-based chemoradiotherapy. Oncologists should be aware of this possible complication to undertake early intervention.

Ovarian adenocarcinoma in a young female with skin and umbilical metastasis

We report the case of ovarian carcinoma with skin and umbilical metastasis in a 30-year-old female. The computed tomography (CT) scan of the abdomen showed a right ovarian mass with anterior abdominal wall metastasis. The CT-guided fine needle aspiration cytology (FNAC) from the ovarian mass showed adenocarcinoma. FNAC from the umbilical and skin metastasis also showed adenocarcinoma. Because of the unresectability of the mass, the patient was put on taxol-based chemotherapy, which she took for two cycles, and then died of progressive disease after three months.

Comparitive study of efficacy, tolerability of four field box technique vs. two field anterior posterior technique in locally advanced carcinoma cervix--a prospective analysis.

Purpose: The pelvic failure rate decreases with increase in the radiation dose but the complications increase. The four field pelvic technique has a theoretical advantage of providing a higher tumor dose with less dose to the surrounding normal tissue thus reducing the complications. Result: Eighty-three patients completed treatment, 42 in Arm A and 41 in Arm B. The complete response achieved in the two groups was 85.75% and 87.8% (p = 0.67). Skin reactions were more in Arm B (p < 0.05). Grade II GIT symptoms were more common in both the groups (p = 0.75). Grade I GUT toxicity was the most common toxicity in both the arms (p = 0.38). The most common hematological toxicity in the two arms was of grade II (p = 0.78). Material and method: After satisfying the eligibility criteria histo-pathologically proven locally advanced carcinoma cancer cervix patients were randomized to four (Arm A) or two (Arm B) field techniques. Conclusions: Both two and four field box techniques are equally effective and feasible as stastically insignificant difference in the response rate and acute toxicities was observed in the two arms.