Punita Lal

Intrarectal formalin application, an effective treatment for grade III haemorrhagic radiation proctitis

Haemorrhagic radiation proctitis (HRP) is infrequently seen amongst the patients who are either undergoing or have undergone radiotherapy to the pelvis. We treated 16 documented cases of HRP, who did not respond to conventional steroid retention enemas, with 4% formalin application. It was observed that the rectal bleeding was controlled completely in 81% cases in median follow up of 11 months (range 6-17 months) and diversion colostomy could be avoided in all the cases. The effectiveness of local formalin application in severe HRP is described in this article.

Role of GSTM3 Polymorphism in the Risk of Developing Esophageal Cancer

GSTM3 is involved in detoxification of carcinogens and may be important in modulating cancer susceptibility. GSTM3 genotype frequencies were determined in peripheral blood DNA of 149 esophageal cancer patients and 200 nonmalignant controls using the PCR followed by PAGE. Patients who were heterozygous carriers of GSTM3 AB genotype had an enhanced risk for developing esophageal cancer [odds ratio (OR), 2.1; 95% confidence interval (95% CI), 1.1-3.7; P = 0.01]. In males, the risk due to GSTM3 AB genotype increased further (OR, 3.4; 95% CI, 1.7-6.8; P = 0.000). Interaction of GSTM3 AB + BB and GSTM1 null genotypes marginally modulated risk (OR, 2.3; 95% CI, 1.1-3.7; P = 0.01). Association with histology (adenocarcinoma: OR, 3.4; 95% CI, 1.1-10.9; P = 0.03) and tumor site (middle third location: OR, 2.2; 95% CI, 1.1-4.4; P = 0.01; lower third location: OR, 2.6; 95% CI, 1.2-5.6; P = 0.01) was also documented. Our results suggest that GSTM3 polymorphism may influence esophageal cancer susceptibility, in particular modulating the risk for adenocarcinoma histology and tumors of the mid and lower third region. (Cancer Epidemiol Biomarkers Prev 2007;16(1):178–81)

Hemostatic radiotherapy in carcinoma of the uterine cervix

Objective: To evaluate the treatment of hemorrhagic carcinoma of the uterine cervix with hemostatic radiotherapy (external and intracavitary radiotherapy). Method: Twenty cases of refractory hemorrhagic carcinoma of the uterine cervix receiving hemostatic radiotherapy between April 1987 and May 1992 were analyzed. The age of the patients ranged between 30 and 60 years with a median of 42 years. Results: The mean tumor volume was 130 mm3; all cases were classified as FIGO stage IIb (n = 8), IIIb (n = 11) or IVa (n = 1). Radiotherapy was carried out either by the external or intracavitary technique. The control of hemorrhage was 100% within 12–48 h after radiotherapy. However 85% of patients failed locally in the form of residual, recurrent pelvic or metastatic disease, within 24 months of follow‐up. Conclusion:Hemorrhagic cervical cancer has a poor prognosis.

Implications of contrast-enhanced CT-based and MRI-based target volume delineations in radiotherapy treatment planning for brain tumors.

Delineation of various target volumes using contrast-enhanced magnetic resonance imaging (MRI) and/or computed tomography (CT) constitutes the primary step for radiation therapy planning (RTP) in brain tumors. This study presents a quantification and comparative evaluation of the various clinical target volumes (CTV) and gross target volumes (GTV) as outlined by contrast-enhanced CT and MRI, along with its implications for postoperative radiotherapy of brain tumors. Twenty-one patients of gliomas were considered for this prospective study. Peritumoral edema as CTV and residual tumor as GTV were delineated separately in postoperative contrast-enhanced CT and MRI. These volumes were estimated separately and their congruence studied for contrast-enhanced CT and MRI. Compared to MRI, CT underestimated the volumes, with significant differences seen in the mean CTV (mean +/- SD: -62.92 +/- 93.99 cc; P = 0.006) and GTV (mean +/- SD: -21.08 +/- 36.04 cc; P = 0.014). These differences were found to be significant for high-grade gliomas (CTV: P = 0.045; GTV: P = 0.044), while they were statistically insignificant for low-grade gliomas (CTV: P = 0.080; GTV: P = 0.117). The mean differences in the volumes for CTV and GTV were estimated to be -106.7% and -62.6%, respectively, taking the CT volumes as the baseline. Thus, even though, electron density information from CT is essential for RTP, target delineation during postoperative radiotherapy of brain tumors, especially for high-grade tumors, should be based on MRI so as to avoid inadvertent geographical misses, especially in the regions of peritumoral edema.

Feasibility Study of Safe Breast Conservation in Large and Locally Advanced Cancers with Use of Radiopaque Markers to Mark Pre-Neoadjuvant Chemotherapy Tumor Margins

BackgroundThe lack of objective documentation of pre-neoadjuvant chemotherapy (NACT) margins after chemotherapy is a major constraint in performing safe breast-conserving surgery (BCS) in patients with locally advanced breast cancer (LABC). Using a novel method of marking pre-NACT tumor margins with indigenous silver wire markers, this prospective pilot study attempted to assess the feasibility of safe BCS in LABC patients by performing excision wide of the marked pre-NACT margins.MethodsLABC patients had sterile silver wire markers placed at all tumor margins percutaneously. Patients were then treated with NACT followed by wide local excision (WLE) incorporating pre-NACT margins (ex vivo on mastectomy specimen or in vivo in patients opting for BCS). The histology of the margins wide of the post-WLE cavity (pre-NACT) and post-NACT tumor was used to assess adequate disease clearance and safety of BCS.ResultsAltogether, 40 stage III breast cancer patients (mean tumor size 7.9 cm) were studied; none had marker-related complications. Following NACT, the tumor size assessed by markers showed average regression by 1.5 cm. The pre-NACT margins were histologically negative in 95% of the surgical specimens. In 2 (5%) patients both pre-NACT and post-NACT margins were positive; post-NACT margins were infiltrated in 14 (35%).ConclusionsThe post-NACT WLE that is wide of the marked pre-NACT margins can achieve uninfiltrated margins in 95% of cases. If post-NACT margins are used to guide the WLE, 35% patients would have infiltrated margins, some of which would remain undetected, putting patients at high risk of local recurrence. This novel indigenous method of identifying tumor margins with sterile silver wire markers is safe, inexpensive, practical, and effective; and it may help perform safe BCS in a large proportion of LABC patients.

Factors influencing the development of ulcers and strictures in carcinoma of the esophagus treated with radiotherapy with or without concurrent chemotherapy

PURPOSE To ascertain factors that could influence the development of ulcers and strictures in the definitive management of squamous cell carcinoma (SCC) of esophagus treated with external beam radiotherapy (EBRT), high-dose-rate (HDR) intralumenal radiotherapy (ILRT) with or without concurrent weekly cisplatin (CDDP @ 35 mg/m2) chemotherapy (CT). MATERIALS AND METHODS Between 1990-2005, 244 patients with inoperable SCC of esophagus were identified from our database and grouped into one of the following: those receiving at least 60 Gy EBRT (Gp E, n=44); EBRT followed by HDR-ILRT (Gp E+I, n=98); at least 50 Gy EBRT with CT (Gp E+C, n=68); EBRT+HDR-ILRT + CT (Gp E+I+C, n=34). Ulcers (discovered on endoscopy) and strictures evident on a barium swallow (which needed dilatations) were scored as treatment induced, if the biopsy was negative. Factors likely to influence their outcome were analyzed. RESULTS The groups were matched for all patient and disease characteristics except pretreatment hemoglobin and Karnofsky performance score (KPS), which were lower in Gp E. The incidence of ulcers was 7%, 8%, 6% and 21% (P=0.08) while that of strictures was 14%, 9%, 21% and 41% (P=0.00) for the groups E, E+I, E+C and E+I+C respectively. On univariate analysis, patients with better KPS (P=0.03), treated with narrow applicators (6 mm vs. 10 mm, P=0.00), received CT (P=0.00) or assigned to Gp E+I+C (P =0.00) were more likely to develop strictures, with a trend for development of ulcers in Gp. E+I+C (P=0.08). Logistic regression retained only Gp E+I+C for development of ulcers (OR 10.36, 95% CI 1.2-89.1, P=0.03) and strictures (OR 4.2, 95% CI 1.4-12.6, P=0.00). CONCLUSION Treatment intensification as in Gp E+I+C results in about a three-fold increase in treatment induced late morbidity which can adversely impact on swallowing function and therefore emphasizes the need for optimisation of HDR-ILRT when used in a CT+RT protocol.

Iridium-192 interstitial brachytherapy in carcinoma of the tongue. The importance of various tumor and physical parameters.

A detailed analysis of host-tumor factors and interstitial physical factors influencing the disease-free control in carcinoma of the tongue was carried out. Twenty-eight cases of carcinoma of the tongue T1-3, NO-1, MO were treated radically with combined external irradiation and 192Iridium interstitial brachytherapy (one patient received brachytherapy only). The teletherapy dose ranged from 44 Gy to 56 Gy (average 48 Gy), the brachytherapy dose ranged from 16 Gy to 55 Gy (average 22 Gy). The interstitial practice involved loop technique in all the cases. Dose distribution analysis to assess factors influencing local control included indices of dose rate, source activity, inter-planar distance, and discontinuity in the prescribed isodose in other planes when compared to mid-plane. Two-year actuarial disease-free survival (DFS) was 46% with primary treatment and 63% when salvage treatment was also included. DFS was significantly poorer when the interplanar distance at mid-plane exceeded 10 mm (p < 0.05). Similarly, tumor control was poorer (p < 0.008) when there was discontinuity in the prescribed isodose in 1 or 2 planes (1 cm superior and inferior to mid-plane). Interplanar distance of around 10 mm, prescribed isodose continuity in all three planes and limiting the dose maximum within a factor of 2 will optimize the results of interstitial implants.

Role of videofluorography in assessing functional abnormalities in patients of head and neck cancer treated with chemoradiotherapy

Aim:  The major toxicity following treatment for head neck cancer is swallowing dysfunction which can be easily assessed by videofluorography (VFG), allowing documentation of the site and extent of abnormality thereby facilitating directed management.

Is aspiration as detected on pretreatment video fluorography, a harbinger of poor quality of life and early mortality in cancers of the upper aerodigestive tract treated with radiotherapy?

Background: Patients with cancers of the upper aerodigestive tract (head and neck cancer (HNC)) tend to aspirate, either due to disease or treatment. The association of aspiration (documented on video fluorography (VFG)) with quality of life (QOL) and unexpected mortality was studied prospectively in patients treated with simultaneous integrated boost technique of intensity-modulated radiotherapy (SIB-IMRT). Materials and Methods: Moderately advanced (stage III/IV) HNC were treated by SIB-IMRT delivering 66 Gy/30 fr, 60 Gy/30 fr, and 54 Gy/30 fr to high, intermediate, and low risk volumes, respectively. They underwent serial VFG and QOL assessments (Quality of Life Questionnaire-Core 30 (QLQ-C30) and head and neck-35 (HN35) European Organisation for Research and Treatment of Cancer (EORTC) tools) at 0, 3, and 6 months. Pharyngeal musculature (PM) was additionally delineated on planning computed tomography (CT) scans as potential organs at risk (OARs). Results: Between November 2009 and May 2011, 20 HNC were treated as per protocol. All patients were fit (Karnofsky performance status (KPS) ≥ 80). Based on VFG findings, seven patients (4/9 oropharynx and 3/11 laryngopharynx) were grouped as aspirators (A) and remaining 13 as non-aspirators (NA). The QOL study showed that pretreatment coughing and swallowing difficulties were greater in group A versus NA and remained persistently higher. In group A, deaths attributable to aspiration were seen in 3/7 patients, while none occurred in the NA group (Fishers exact P = 0.03). The mean PM dose was 60 Gy in both the groups and mean V60 was similar at 69 and 67% in A and NA groups, respectively. Conclusions: VFG helps identify patients who aspirate and are at risk of premature death due to its complications, alerting caregivers to direct attention appropriately.

Intensity-modulated radiotherapy in head and neck cancers: In which direction are we heading?

Radiotherapy (RT) is one of the treatment modalities, which most of the time used in the treatment of most head and neck cancers with/without chemotherapy either as a definitive treatment or adjuvant/postoperated or for symptoms palliation, but it is always accompanied by late sequelae such as xerostomia and dysphagia. These two major sequelae have a significant effect on patient′s quality of life even after cure of disease. However, with the advancement of modern techniques such as intensity-modulated RT (IMRT) which effectively spares the parotid glands has a significant effect, proven in randomized trials, for xerostomia as well as dysphagia. IMRT to spare dysphagia and aspiration related structure ( DARSs) has also been studied extensively. To improve the results further, nowadays, we focus on use of functional imaging at the time of RT planning and/or use of image guidance for the adaptation during RT treatment as well as focus on to reduce neurocognition effects of treatment by sparing brain.