Tirath Nijjar

Oligodendroglioma. The princess margaret hospital experience (1958–1984)

Background. Oligodendrogliomas are rare central nervous system (CNS) tumors. Although surgery remains the primary treatment, the role of postoperative radiation treatment remains a matter of controversy. This study assesses whether postoperative radiation improves survival and local tumor control when compared with surgical treatment alone.

A treatment planning study comparing helical tomotherapy with intensity-modulated radiotherapy for the treatment of anal cancer

PURPOSE A planning study to compare helical tomotherapy (HT) and intensity-modulated radiotherapy (IMRT) for the treatment of anal canal cancer. MATERIALS AND METHODS Sixteen (8 males and 8 females) patients with anal cancer previously treated radically were identified. HT and IMRT plans were generated and dosimetric comparisons of the plans were performed. The planning goals were to deliver 54Gy to the tumor (PTV(54Gy)) and 48Gy to the nodes at risk (PTV(Node)) in 30 fractions. RESULTS PTVs: HT plans were more homogeneous for both men and women. Male patients: HT vs. IMRT: D(max): 55.87+/-0.58 vs. 59.17+/-3.24 (p=0.036); D(min): 52.91+/-0.36 vs. 44.09+/-6.84 (p=0.012); female patients: HT vs. IMRT: D(max): 56.14+/-0.71 vs. 59.47+/-0.81 (p=0.012); D(min): 52.36+/-0.87 vs. 50.97+/-1.42 (p=0.028). OARs: In general, HT plans delivered a lower dose to the peritoneal cavity, external genitalia and the bladder and IMRT plans resulted in greater sparing of the pelvic bones (iliac crest/femur) for both men and women. Iliac crest/femur: the difference was significant only for the mean V10Gy of iliac crest in women (p< or =0.012). External genitalia: HT plans achieved better sparing in women compared to men (p< or =0.046). For men, the mean doses were 18.96+/-3.17 and 15.72+/-3.21 for the HT and IMRT plan, respectively (p< or =0.017). Skin: both techniques achieved comparable sparing of the non-target skin (p=NS). CONCLUSIONS HT and IMRT techniques achieved comparable target dose coverage and organ sparing, whereas HT plans were more homogeneous for both men and women.

Prospective phase II study of tomotherapy based chemoradiation treatment for locally advanced anal cancer

BACKGROUND AND PURPOSE To evaluate toxicity, local control, and survival of anal cancer patients treated with helical tomotherapy (HT) and concurrent 5-fluorouracil and mitomycin-C (5FU/MMC). MATERIALS AND METHODS Fifty-seven patients were treated with HT and concurrent 5FU/MMC. The planning objectives were to deliver 54 Gy to the tumor (PTV54) and 45 Gy to the nodes at risk (PTV45) in 30 fractions. Patients were reviewed for toxicity weekly during HT, every 6 weeks for 3 months, and then every 3-4 months for 5 years. RESULTS The median follow-up was 40 months. The median age was 58 years (range: 37-83). Stage distribution: stage II-48%, IIIA-18%, IIIB-34%. The majority of patients developed ⩽ grade 2 acute toxicity scores. The most common ⩾ grade 3 acute toxicity was neutropenia (40%). Common late toxicities were grade 2 anal incontinence (16%) and telangiectasia (12%). The 3 year colostomy-free survival rate was 77% (95% CI: 61-87%), 3 year disease-free survival rate was 80% (CI: 66-89%), and 3 year overall survival was 91% (CI: 77-96%). CONCLUSIONS Incorporation of HT with concurrent 5FU/MMC had low treatment-related acute and late morbidity with few treatment breaks. However, the expected dosimetric benefit for hematological toxicity was not experienced clinically.

Patient reported quality of life after helical IMRT based concurrent chemoradiation of locally advanced anal cancer

BACKGROUND AND PURPOSE Concurrent chemoradiation (CCRT) is the standard treatment for locally advanced anal canal carcinoma, although treatment-related side effects can affect patient quality of life (QOL). The purpose was to prospectively evaluate the effects of Tomotherapy (HT) based CCRT on patient reported QOL in locally advanced anal cancer. PATIENTS AND METHODS Fifty-four patients treated with HT and concurrent 5-fluorouracil/mitomycin-C underwent QOL evaluation at baseline, after treatment, and during follow-up with EORTC core (QLQ-C30) and colorectal (QLQ-CR29) questionnaires. The QOL scores at baseline and post-treatment were compared. RESULTS All C30 functional symptoms, except emotional and cognitive functioning, were impaired end-of-treatment and recovered by 3months follow-up. The majority of symptom scores were worse end-of-treatment but recovered by 3months except for fecal incontinence (FI), diarrhea, urinary incontinence (UI), and dyspareunia which persisted. FI returned to baseline at 12months while diarrhea, UI, and dyspareunia persisted. CONCLUSIONS Most impaired functions and symptoms following HT based CCRT were temporary and improved by 3months post-therapy. Late complications affecting QOL were FI, sexual function, UI, and diarrhea. Our observations support routine use of IMRT and emphasize the significance of precise evaluation of sexual, urinary, and anorectal functions before starting CCRT and routine incorporation of QOL evaluations.

MicroRNA expression profiling of sputum for the detection of early and locally advanced non-small-cell lung cancer: a prospective case–control study

BACKGROUND Non-small-cell lung cancer (nsclc) is associated with very poor overall survival because 70% of patients present with locally advanced or metastatic disease at the time of diagnosis. Micrornas (mirnas) are a class of short, noncoding rna molecules whose presence in samples of biologic fluids such as sputum has demonstrated promise as a potential means of detecting nsclc. We investigated the stage-specific nsclc detection potential of an efficient panel of 3 mirnas (mir-21, mir-210, mir-372) using a single sputum sample. METHODS A single spontaneously expectorated sputum sample was prospectively collected from 21 early nsclc (≤stage ii) patients, 22 advanced nsclc (≥stage iii) patients, and 10 control subjects. Mirna expression profiles were determined by quantitative real-time polymerase chain reaction and were analyzed by unsupervised hierarchical cluster analysis. RESULTS Mean tumour size (±95% confidence interval) in the early and advanced nsclc patients was 3.3 cm ± 0.9 cm and 4.8 cm ± 0.7 cm respectively. Adenocarcinoma constituted 61.9% of the early and 45.5% of the advanced nsclc cases respectively. In comparing the early nsclc group with the control group, the mirna panel yielded a diagnostic sensitivity of 67% and a specificity of 90.0%. For the advanced nsclc group, the mirna panel detected nsclc with a sensitivity and specificity of 64% and 100% respectively. CONCLUSIONS A sputum mir-21, mir-210, and mir-372 expression profile might provide a sensitive and highly specific means for detecting nsclc. Sputum mirna analysis demonstrates promise as a potential complementary screening tool.

Dose-escalated Hypofractionated Intensity-modulated Radiation Therapy With Concurrent Chemotherapy for Inoperable or Unresectable Non-small Cell Lung Cancer

Purpose: The local control of inoperable non-small cell lung cancer (NSCLC) using standard radiotherapy (RT) doses is inadequate. Dose escalation is a potential strategy to improve the local control for patients with NSCLC; however, the optimal dose required for local control in this setting is unknown. Methods and Materials: Patients with unresectable or inoperable stage II/III NSCLC with ECOG⩽1 received 48 Gy in 20 daily fractions using intensity-modulated radiotherapy, followed by 1 of 3 boost dose levels: 16.8 Gy/7 (cumulative 2 Gy equivalent dose [EQD2]≅76 Gy/38), 20.0 Gy/7 (EQD2≅84 Gy/42), and 22.7 Gy/7 (EQD2≅92 Gy/46). Two cycles of cisplatin/etoposide chemotherapy were given concurrent with RT. The maximum tolerated dose was defined as the dose at which ≥30% experienced dose-limiting toxicity (any NCIC Common Terminology for Adverse Events V3.0 grade 3 or higher acute toxicity). Results: Twelve patients completed treatment with a median follow-up of 22 months (range, 7 to 48). The median age was 72 (range, 54 to 80) and 50% of patients had adenocarcinoma. Five, 3, and 4 patients were treated on dose levels 1, 2, and 3, respectively. No dose-limiting toxicity was observed. One-year local progression-free survival and overall survival estimates were 81% and 58%, respectively. Conclusions: Hypofractionated intensity-modulated radiotherapy was well tolerated and provided meaningful local control for patients with locally advanced inoperable NSCLC. The maximum tolerated dose of RT in this setting lies beyond an EQD2 of 92 Gy/46 and further dose escalation in this setting is warranted.

Palliative chemoradiotherapy versus radiotherapy alone for dysphagia in advanced oesophageal cancer: a multicentre randomised controlled trial (TROG 03.01)

BACKGROUND A short course of radiotherapy is commonly prescribed for palliative relief of malignant dysphagia in patients with incurable oesophageal cancer. We compared chemoradiotherapy with radiotherapy alone for dysphagia relief in the palliative setting. METHODS This multicentre randomised controlled trial included patients with advanced or metastatic oesophageal cancer who were randomly assigned (1:1) through a computer-generated adaptive biased coin design to either palliative chemoradiotherapy or radiotherapy alone for treatment of malignant dysphagia at 22 hospitals in Australia, Canada, New Zealand, and the UK. Eligible patients had biopsy-proven oesophageal cancer that was unsuitable for curative treatment, symptomatic dysphagia, Eastern Cooperative Oncology Group performance status 0-2, and adequate haematological and renal function. Patients were stratified by hospital, dysphagia score (Mellow scale 1-4), and presence of metastases. The radiotherapy dose was 35 Gy in 15 fractions over 3 weeks for patients in Australia and New Zealand and 30 Gy in ten fractions over 2 weeks for patients in Canada and the UK. Chemotherapy consisted of one cycle of intravenous cisplatin (either 80 mg/m2 on day 1 or 20 mg/m2 per day on days 1-4 of radiotherapy at clinicians discretion) and intravenous fluorouracil 800 mg/m2 per day on days 1-4 of radiotherapy in week 1. Patients were assessed weekly during treatment. The primary endpoint was dysphagia relief (defined as ≥1 point reduction on the Mellow scale at 9 weeks and maintained 4 weeks later), and key secondary endpoints were dysphagia progression-free survival (defined as a worsening of at least 1 point on the Mellow scale from baseline or best response) and overall survival. These endpoints were analysed in the intention-to-treat population. This study is registered at ClinicalTrials.gov, number NCT00193882. This trial is closed. FINDINGS Between July 7, 2003, and March 21, 2012, 111 patients were randomly assigned to chemoradiotherapy and 109 patients to radiotherapy. One patient in the chemoradiotherapy group was omitted from analysis because of ineligibility. 50 (45%, 95% CI 36-55) patients in the chemoradiotherapy group and 38 (35%, 26-44) in the radiotherapy group obtained dysphagia relief (difference 10·6%, 95% CI -2 to 23; p=0·13). Median dysphagia progression-free survival was 4·1 months (95% CI 3·5-4·8) versus 3·4 months (3·1-4·3) in the chemoradiotherapy and radiotherapy groups, respectively (p=0·58), and median overall survival was 6·9 months (95% CI 5·1-8·3) versus 6·7 months (4·9-8·0), respectively (p=0·88). Of the 211 patients who commenced radiotherapy, grade 3-4 acute toxicity occurred in 38 (36%) patients in the chemoradiotherapy group and in 17 (16%) patients in the radiotherapy group (p=0·0017). Anaemia, thrombocytopenia, neutropenia, oesophagitis, diarrhoea, nausea and vomiting, and mucositis were significantly worse in patients who had chemoradiotherapy than in patients who had radiotherapy. INTERPRETATION Palliative chemoradiotherapy showed a modest, but not statistically significant, increase in dysphagia relief compared with radiotherapy alone, with minimal improvement in dysphagia progression-free survival and overall survival with chemoradiotherapy but at a cost of increased toxicity. A short course of radiotherapy alone should be considered a safe and well tolerated treatment for malignant dysphagia in the palliative setting. FUNDING National Health and Medical Research Council, Canadian Cancer Society Research Institute, Canadian Cancer Trials Group, Trans Tasman Radiation Oncology Group, and Cancer Australia.

Palliative whole brain radiotherapy: Predictors of prescribing 5 versus 10 fractions.

219 Background: The optimal dose for palliative whole brain radiotherapy (WBRT) continues to be debated. Common regimens include 20 Gy in five and 30 Gy in 10 fractions. We aimed to identify factors associated with WBRT dose schedules, hypothesizing that clinical prediction of survival (CPS) would influence prescribing practice. METHODS Demographic and clinicopathologic data were collected for consecutive patients with brain metastases receiving WBRT through a dedicated palliative radiation oncology clinic. At initial consultation, CPS were prospectively collected from treating radiation oncologists. Karnofsky performance status (KPS) and Mini-Mental Status Examination were available for 88.6% and 75.1%, respectively. Dose fractionation was collected and summary statistics calculated. Parameters were assessed for association with five fraction schedules using binary logistic regression, with odds ratios and 95% CI reported. RESULTS 193 patients underwent WBRT (N = 102 from 2010-2012; N = 91 from 2013-2014); 38/193 had 48 extracranial sites irradiated concurrently. 46.1% were male, mean age was 64.7 years (SD 11.6), and 63.7% had lung cancer. Median KPS was 70 (range 20-100) and median MMSE score was 27/30 (range 13-30). Median CPS and actual survival were 150 days (range 21-730d) and 96 days (range 11-1029d), respectively. 18.7% received WBRT within 30 days of death. 78.2% (151/193) and 17.6% (34/193) received five and 10 fractions, respectively; 8/193 were prescribed other schedules. On multivariate analysis, patients with KPS ≤ 70 were 5.93 times more likely to have received 5-fractions (95% CI 2.51-14.1; p < 0.0001). Those treated 2010-2012 were less likely to have received 5 fractions (OR 0.28; 95% CI 0.11-0.68; p = 0.005). CPS, age, gender, MMSE, histology, disease extent, and extracranial irradiation were not predictive of WBRT schedule. CONCLUSIONS Patients treated with WBRT with KPS ≤70 and those treated more recently were more likely to receive five fractions. Oncologist CPS was not a statistically significant predictor of schedule in this cohort.

Does expected survival influence palliative radiotherapy treatment recommendations

35 Background: Survival is often overestimated, yet physicians rely on such predictions to recommend appropriate therapy and assist with end-of-life planning. Administration of radiotherapy (RT) within the last 30 days of life has been suggested as an indicator of poor quality care, since acute side effects reduce quality of life with insufficient time for symptomatic benefit. We investigated whether life expectancy predicted at the time of consultation correlates with palliative RT recommendations. METHODS Radiation oncologists from a dedicated palliative Radiation Oncology outpatient clinic anonymously completed survival estimations after clinical assessment, and recorded factors upon which each estimate was based. Demographics, primary histology, RT details, and date of death were abstracted. Summary statistics and Kaplan-Meier estimates of actual survival (AS) were obtained. Correlations between AS and clinical predictions of survival (CPS) were calculated using Spearmans correlation coefficient (r). Multivariate logistic regression analysis explored factors associated with RT recommendations. RESULTS 476 survival predictions were made for 420 unique patients (06/2010-01/2014). Median age was 67.7 years, 61.9% were male and 44.0% had lung cancer. Karnofsky Performance Status (KPS) was > 70 at 23.9% of clinic visits. At 84.5% of consultations, RT was prescribed to 538 separate volumes (29.2% receiving 8Gy, 54.8% 20Gy, 6.3% 30Gy, 9.7% other). Mean AS was 179 days (SD 187d), moderately correlating with mean CPS of 242 days (SD 261d) with r = 0.38 (p < 0.0001). Factors most frequently cited as influencing CPS were KPS and extent of disease. At the time of 30/476 visits, CPS was < 30 days; at 19 of these visits, RT was prescribed to 26 volumes (21 bone, 3 whole brain, 2 chest), 2/3 as single fractions, finishing a median of 17 days before death. Expected survival was predictive of prescribed RT dose on univariate logistic regression, but did not retain significance on multivariate analysis. CONCLUSIONS Despite international surveys in which prognosis has been cited as the main factor affecting treatment decisions, in this cohort, other aspects appear to have more strongly influenced palliative RT recommendations.

Quality of life (QoL) in patients with malignant dysphagia: An international randomized trial comparing radiotherapy alone (RT) versus chemoradiotherapy (CRT)—TROG03.01 NCICCTG ES2.

163 Background: The dominant symptom for pts with esophageal cancer is dysphagia. Palliative radiotherapy is commonly employed for symptom relief. We report the effect on QoL in our study comparing a 2-3 week course of RT alone vs the same RT with a single cycle of concomitant CT. METHODS 220 pts with malignant dysphagia were randomized to receive RT (30-35Gy in 10-15 fr) (n=109) ± concomitant CT (5FU and cisplatin D1-4) cycle. The primary outcome was dysphagia relief. QoL was evaluated using EORTC QLQ30/OES18 at baseline, wk 9, 13 and mthly x1yr. Group mean scores were compared between arms using Wilcoxon Rank-Sum test. Proportion of pts with improved, stable or worsened QoL (≥10 point change at any time compared with baseline) using chi square and MH chi-square test (for trend), while time to dysphagia improvement was compared using K-M estimates. RESULTS QoL compliance ranged from 77% (169/220) at baseline to 62% (36/58) at mth12 and was similar between groups. Baseline mean scores were equivalent between arms with the exception of physical [79 (SD19) CRT vs. 83.84 (SD19) RT; p=0.016] and role domains [61 (SD34) CRT vs. 72 (SD32) RT; p = 0.01]. There was no significant difference in QoL between the arms. The proportion of pts with improvement in the dysphagia domain was 50% CRT vs 64% RT (ns) while the time to improvement was 2.6m CRT vs 2.3m RT (ns). The eating domain was improved in 68% CRT and 74% RT (ns) while global QoL was 46% in both arms. Other symptom domains/items that were improved in more than half of the pts included 62% in pain and 52% in appetite. Functional domain improvements were moderate ranging from 41% emotional, 39% role, 38% social, 28% cognitive to 18% physical (average of scores in both arms). CONCLUSIONS QoL data showed improvement in domains associated with nutritional intake for 50-70% of pts depending on the symptom measured. This was accompanied by moderate improvement in functional domains. No significant benefit was observed when CT was added to RT alone. CLINICAL TRIAL INFORMATION NCT00193882.