HPV screening for cervical cancer in rural India.

BACKGROUND: In October 1999, we began to measure the effect of a single round of screening by testing for human papillomavirus (HPV), cytologic testing, or visual inspection of the cervix with acetic acid (VIA) on the incidence of cervical cancer and the associated rates of death in the Osmanabad district in India. METHODS: In this cluster-randomized trial, 52 clusters of villages, with a total of 131,746 healthy women between the ages of 30 and 59 years, were randomly assigned to four groups of 13 clusters each. The groups were randomly assigned to undergo screening by HPV testing (34,126 women), cytologic testing (32,058), or VIA (34,074) or to receive standard care (31,488, control group). Women who had positive results on screening underwent colposcopy and directed biopsies, and those with cervical precancerous lesions or cancer received appropriate treatment. RESULTS: In the HPV-testing group, cervical cancer was diagnosed in 127 subjects (of whom 39 had stage II or higher), as compared with 118 subjects (of whom 82 had advanced disease) in the control group (hazard ratio for the detection of advanced cancer in the HPV-testing group, 0.47; 95% confidence interval [CI], 0.32 to 0.69). There were 34 deaths from cancer in the HPV-testing group, as compared with 64 in the control group (hazard ratio, 0.52; 95% CI, 0.33 to 0.83). No significant reductions in the numbers of advanced cancers or deaths were observed in the cytologic-testing group or in the VIA group, as compared with the control group. Mild adverse events were reported in 0.1% of screened women. CONCLUSIONS: In a low-resource setting, a single round of HPV testing was associated with a significant reduction in the numbers of advanced cervical cancers and deaths from cervical cancer.

Factors affecting the quality of voice in the early glottic cancer treated with radiotherapy.

AIMS: To prospectively analyze the objective voice quality before and after radiotherapy (RT) for early glottic cancer and to evaluate the role of different factors that may affect it. METHODS: Patients with T1-T2N0M0 glottic cancer underwent voice quality assessment before treatment and after radical RT. Post-RT voice quality was compared to the voice at diagnosis and the voice of healthy individuals used as controls. A comprehensive set of voice parameters were measured. The effects of age, smoking history, T stage, anterior commissure (AC) involvement, radiation dose, fractionation and volumes on pre-treatment and post-treatment voice quality were analyzed. RESULTS: The voice quality data of 50 patients were analyzed. Following treatment, there was a significant improvement in the majority of measured parameters. However, perturbation and HNR remained inferior compared to controls. A history of smoking, AC involvement and larger RT volumes resulted in poorer voice parameters following RT. There was no significant impact of age alone. T2 tumors had an inferior voice quality before treatment, but did not remain inferior following RT. Hypofractionated RT did not show any negative impact. CONCLUSIONS: There is a considerable improvement of voice quality following RT. Several factors may have specific effects on pre-treatment and post-treatment voice.

Squamous cell carcinoma of the hypopharynx: single-institution outcome analysis of a large cohort of patients treated with primary non-surgical approaches.

INTRODUCTION: Hypopharyngeal cancers have extensive submucosal spread, high risk of nodal involvement and relatively high propensity of distant metastases. Contemporary paradigms for hypopharyngeal cancers aim to maximize loco-regional control while attempting to preserve laryngo-pharyngeal form and function. AIMS: To retrospectively review outcome of large cohort of patients with hypopharyngeal cancers treated with curative intent radiotherapy with or without systemic chemotherapy in an academic tertiary referral centre. MATERIAL AND METHODS: Medical records of patients with hypopharyngeal cancers treated with primary non-surgical approaches over a 15-year period were reviewed retrospectively. Loco-regional control (LRC) and disease-free survival (DFS) were considered as outcome measures. RESULTS: Electronic search of database identified 501 patients with hypopharyngeal cancers treated with definitive radiotherapy. The median age was 55 years (range 20-87 years) and median radiotherapy dose 70 Gy (range 5.4-72 Gy). With a mean follow-up period of 22 months (median 12 months), the 3-year LRC and DFS was 47.1% and 40.9% respectively. Stage (T-stage, N-stage, overall stage grouping), and age influenced outcome significantly. The 3-year LRC for T1-T2 disease was 49.7% versus 43.1% for T3- T4 stage (p0.056). The 3-year DFS was 49.4% and 36.9% respectively (p0.014). The 3-year LRC and DFS for N0; N1; and N2-3 disease was 57.3% & 54.3%; 40.5% & 35.3%; and 33% & 27% respectively with highly significant p-values. CONCLUSION: This is an outcome analysis of the largest cohort of patients with hypopharyngeal cancers managed with primary non-surgical approaches. Stage and age remain the most important determinants of outcome.

Prognostic factors in oropharyngeal cancer--analysis of 627 cases receiving definitive radiotherapy.

INTRODUCTION: The aim of this retrospective analysis was to analyze the results of conventional radical radiotherapy in the treatment of oropharyngeal cancer and to identify pre-treatment and treatment-related prognostic factors for outcome. MATERIAL AND METHODS: The records of 627 patients with oropharyngeal cancer treated with radical radiotherapy with conventional techniques were analyzed. RESULTS: The median age was 56 years. History of tobacco abuse was present in 80.5%. Eighty six percent had stage III or IV disease. Radical radiotherapy alone was the treatment modality for 71.2% and concomitant or neoadjuvant chemotherapy was used in 28.8%. The 3-year local control (LC), loco-regional control (LRC), disease-free survival (DFS) and overall survival (OS) was 49%, 40.6%, 38.9% and 36.1% respectively. The 3-year DFS rates were 80.3% for stage I, 65.8% for stage II, 46.1% for stage III and 25.2% for stage IV disease. Multivariate analysis was performed for prognostic factors. Prior history of tobacco abuse was an independent prognostic factor for both DFS and LRC. Karnofsky Performance Score (KPS) < 80, higher nodal stage, lower total radiotherapy dose (<66 Gy) in those receiving > 60 Gy, and overall treatment time > 50 days were other independent prognostic factors for inferior DFS and LRC. KPS < 80, higher T stage, higher nodal stage, RT dose < 66 Gy and longer overall treatment time (>50 days) were independent prognostic factors for poorer local control. CONCLUSIONS: Several patient-, disease- and treatment-related variables independently affect survival outcomes after radical radiotherapy for oropharyngeal cancer. Oropharyngeal cancers in those without a history of tobacco abuse may be biologically different and more amenable to cure with radiotherapy.

Estimation of risk of radiation-induced carcinogenesis in adolescents with nasopharyngeal cancer treated using sliding window IMRT.

PURPOSE: To estimate the risk of radiation-induced carcinogenesis based on whole-body dose measurement on adolescent patients undergoing intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Ten adolescent patients with nasopharyngeal cancer were planed and treated to a dose of 70.2 Gy using sliding window IMRT. Peripheral dose (PD) was measured using thermoluminescent dosimeters kept at anterior, lateral and posterior positions of each axial plane at the level of xiphoid process, umbilicus and gonads of every patient. The associated risk of radiation-induced carcinogenesis was estimated based on the measured whole-body dose and using age- and sex-specific ICRP-60 nominal probability coefficient of 7.5% (boys) and 9.5% (girls) per Sv. RESULTS: In all patients, measured PD per monitor unit (MU) decreases almost exponentially with out-of-field distance and varies with gantry angle. Highest whole-body dose equivalent ranged from 0.5318 to 0.9867 Sv (mean=0.8141 Sv, SD=0.138) which was measured posteriorly at the level of xiphoid process. Whole-body dose was represented by the average dose at xiphoid process and all measurement positions ranged from 0.3661 to 0.8766 Sv (mean=0.658 Sv, SD=0.16) and 0.2267 to 0.5277 Sv (mean=0.3859 Sv, SD=0.09), respectively. The associated mean risk of radiation-induced carcinogenesis estimated based on different representation of mean whole-body dose was 6.57%, 5.3% and 3.11%, respectively. Higher mean risk of 7.32% was estimated among girls as compared to 6.25% for boys. CONCLUSIONS: Knowledge of risk of secondary malignancy is particularly important in adolescents and should be considered when choosing the optimal treatment technique and delivery system.

Prognostic factors in node negative premenopausal women treated with breast conserving therapy without adjuvant systemic therapy.

PURPOSE: To study the prognostic factors in node negative premenopausal women treated with breast conserving therapy (BCT) without any adjuvant systemic therapy. METHODS: Of the 1022 women treated with BCT at Tata Memorial Hospital, there was a cohort of 175 women who were premenopausal, node negative and had not received any adjuvant systemic therapy. BCT consisted of wide excision, complete axillary clearance, whole breast radiotherapy (45 Gy in 25 fractions) with 6 MV photons plus tumour bed boost either with brachytherapy or electrons. RESULTS: The median age at presentation was 38 years (range 22-51 years) and the median pathological tumour size was 3 cm (1-5 cm). The 5-year actuarial local control rate was 89.5% and the overall survival (OS) was 88%. On univariate analysis, lymphovascular invasion (LVI) was the only prognostic factor affecting all failures and disease-free survival. The 5-year local control rate in absence of LVI was 93.5% in contrast to 76.5% (p=0.0098) when LVI was present. Similarly, the OS in absence of LVI was 91% in contrast to 74% in presence of LVI (p=0.02). On multivariate analysis, LVI was the independent prognostic factor affecting the disease-free survival (p=0.001; 95% CI: 1.46-4.96). CONCLUSION: LVI emerged as the most important prognostic factor for node negative premenopausal women not receiving adjuvant systemic therapy. There is a need to take into consideration the presence of LVI while deciding adjuvant systemic therapy in T1N0 patients.

Profile of prognostic factors in 1022 Indian women with early-stage breast cancer treated with breast-conserving therapy.

PURPOSE: The outcome of breast cancer treatment can vary in different geographic and ethnic groups. A multivariate analysis was performed for various prognostic factors in 1022 Indian women with pathologic Stage I-II breast cancer treated between 1980 and 2000 with standard breast-conserving therapy with or without systemic adjuvant therapy. METHODS AND MATERIALS: At a mean follow-up of 53 months, the outcomes studied were local failure, locoregional failure, and distant failure, overall survival (OS), and disease-free survival (DFS). RESULTS: The median pathologic tumor size was 3 cm (range, 1-5 cm), and axillary lymph node metastasis was present in 39% of women. The actuarial 5- and 10-year OS and DFS rate was 87% and 77% and 76% and 68%, respectively. Lymphovascular emboli or invasion (LVI) was the strongest independent adverse factor for all failure and survival (local failure, hazard ratio 2.85; 95% confidence interval, 1.68-4.83; OS; hazard ratio, 2.01, 95% confidence interval, 1.35-2.99). Lymph node metastasis was also an independent adverse factor for local failure, locoregional failure, distant failure, DFS, and OS (hazard ratio, 1.55, 95% confidence interval, 1.04-2.30). Age < or =40 years increased the incidence of local recurrence, and patients with inner quadrant tumors had inferior DFS. The incidence of LVI was significantly greater in women with lymph node metastases than in node-negative women (p < 0.001) and in women with Grade 3 tumors than in those with Grade 1 or 2 tumors (p = 0.001). CONCLUSION: In Indian women, LVI was the strongest independent prognostic factor for OS, DFS, and local recurrence, irrespective of nodal status and systemic adjuvant treatment. Although LVI may not be a contraindication for BCT, as has been proposed by certain groups, it is necessary to define its role in prospective studies in determining local and systemic treatment.

HIV infection and invasive cervical cancers, treatment with radiation therapy: toxicity and outcome.

BACKGROUND AND PURPOSE: To determine the effect of radiotherapy in HIV seropositive cervical cancer patients, tumour response and toxicity and compliance of patients to the treatment. PATIENTS AND METHODS: This study is a retrospective review of 42 HIV seropositive patients diagnosed with carcinoma cervix, between 1997 and 2003 at the Tata Memorial Hospital. The age and symptoms of presentation, clinical stage, response, compliance and tolerance to radiotherapy were studied. RESULTS: Mean age at presentation was 41 years. All patients presented with the symptoms of cervical disease. Of these patients 31(74%) patients had 'Karnofsky Performance Scale' (KPS) more than 80%. Twenty-one (50%) of the patients were of Stage IIIb-IVa. Thirty-two (76%) were started on radiotherapy with radical intent. Compliance to radiotherapy was poor with 24% patients discontinuing after few fractions of radiotherapy. Seven (17%) patients were given palliative radiotherapy. Twenty-two patients completed prescribed radical radiotherapy and 50% of these achieved complete response. Grade III-IV acute gastrointestinal toxicity was seen in 14% of the patients, and grade III acute skin toxicity was seen in 27% of patients, leading to treatment delays. There was good relief of symptoms in patients treated with palliative intent. CONCLUSIONS: Radiotherapy is effective in this set of patients. Palliative fractionation schedules are effective for patients with poor performance status and locally advanced cancers in relieving the symptoms related to carcinoma cervix. An emphasis should be given to the increased acute mucosal and skin toxicity and to improving compliance and clinical outcome of these patients.

Females with paired occurrence of cancers in the UADT and genital region have a higher frequency of either Glutathione S-transferase M1/T1 null genotype.

Upper Aero digestive Tract (UADT) is the commonest site for the development of second cancer in females after primary cervical cancer. Glutathione S-transferase (GSTM1 and / or T1) null genotype modulates the risk of developing UADT cancer (primary as well as second cancer). The aim of this study was to evaluate the difference in GST null genotype frequencies in females with paired cancers in the UADT and genital region as compared to females with paired cancers in the UADT and non-genital region. Forty-nine females with a cancer in the UADT and another cancer (at all sites-genital and non-genital) were identified from a database of patients with multiple primary neoplasms and were analyzed for the GSTM1 and T1 genotype in addition to known factors such as age, tobacco habits, alcohol habits and family history of cancer. Frequencies of GSTM1 null, GSTT1 null, and either GSTM1/T1 null were higher in females with paired occurrence of cancer in the UADT and genital site (54%, 33% and 75% respectively) in comparison to females with paired occurrence of cancer in the UADT and non-genital sites (22%, 6% and 24% respectively). The significantly higher inherited frequency of either GSTM1/T1 null genotype in females with a paired occurrence of cancers in UADT and genital region (p = 0.01), suggests that these females are more susceptible to damage by carcinogens as compared to females who have UADT cancers in association with cancers at non-genital sites.

Palliation of advanced/recurrent esophageal carcinoma with high-dose-rate brachytherapy.

PURPOSE: The aim was to assess the improvement in swallowing status, complication rate, and overall survival. PATIENTS AND METHODS: Fifty-eight patients with advanced/recurrent esophageal carcinoma were treated for palliation with high-dose-rate intraluminal brachytherapy (HDR-ILRT) with a remote afterloading microSelectron unit (192Ir source) with or without external radiation from November 1994 to May 2000 at the Tata Memorial Hospital. The mean age was 64 years. The mid-third of the esophagus was involved in 38 patients (66%). The group was comprised of 37 previously untreated patients (29 with < or = 50% Karnofsky performance status and old age, 4 with metastatic disease, and 4 with second primary esophageal lesions) and 21 patients with post-treatment recurrent tumors. Thirty-eight patients (65%) received intraluminal brachytherapy alone, whereas the remaining 20 patients (35%) received a combination of external and intraluminal radiation therapy. All patients received 2 fractions of HDR-ILRT 1 week apart with 600 cGy per fraction at 1 cm off axis. RESULTS: Overall improvement in swallowing status was seen in 22 patients (48%), and 24 (41%) maintained pretreatment swallowing status. Median dysphagia-free survival was 10 months. Overall complication rates were 30%, with stricture seen in 9 patients (15%), ulceration in 6 (10%), and tracheo-esophageal fistula in 3 patients (5%). Complication rates were higher in the post-treatment group (38%) than in the previously untreated group (27%) (p = 0.29). The median overall survival for the entire group was 7 months. Median survival was better, although not significantly, for the previously untreated cohort: 7.8 months vs. 6 months for the post-treatment group (p = 0.77). CONCLUSION: HDR-ILRT brachytherapy achieves good palliation with acceptable complications in advanced/recurrent esophageal carcinoma.

Can 99mTc-DTPA aerosol scanning predict radiation pneumonitis?

PURPOSE: To investigate whether changes in diethylenetriamine pentaacetic acid (DTPA) aerosol clearance lung scans predict the development of radiation pneumonitis. METHODS AND MATERIALS: Thirty-three patients with advanced non-small-cell lung cancer were treated with palliative radiation therapy to thorax. All patients were subjected to pretreatment and post-treatment DTPA aerosol clearance lung scans. The clearance t1/2 values were compared using the paired t test. Changes in percentage aerosol deposition were also compared. The patients were serially assessed clinically and radiologically for development of radiation pneumonitis. RESULTS: For the whole group, the mean DTPA clearance t1/2 for the diseased lung fell from 36.33 to 28.85 min (p = 0.17). Twelve patients developed radiation pneumonitis, 8 Grade 1, 2 Grade 2, 1 Grade 3, and 1 Grade 4. In patients who developed radiation pneumonitis, the clearance t1/2 for the diseased lung decreased from 37.50 min to 29.00 min after treatment (p = 0.50). Other subgroups analyzed, including smokers, nonsmokers, those with and without endobronchial disease, as well as those free from radiation pneumonitis, also showed no significant change in the clearance of the aerosol. The difference between the percentage aerosol deposition of the diseased lung (37.92%) and that of the opposite lung (62.08%) for the entire sample was significantly different both before and after treatment (p < 0.01). Delivery of radiation did not significantly change the aerosol deposition in either lung. CONCLUSIONS: We conclude that, in patients with advanced non-small-cell lung cancer, significant change in the pulmonary clearance of 99mTc-DTPA aerosol could not be demonstrated after radiation therapy. In such patients, clearance of the aerosol does not predict the development of radiation pneumonitis.

Nasopharyngeal carcinoma in children: ten years' experience at the Tata Memorial Hospital, Mumbai.

PURPOSE: To evaluate the disease characteristics and outcome of children with nasopharyngeal carcinoma treated at the Tata Memorial Hospital, Mumbai. METHODS AND MATERIALS: Between 1990 and 2000, 81 pediatric patients with a diagnosis of nasopharyngeal carcinoma were treated at the Tata Memorial Hospital. The median age was 14 years. The male/female ratio was 2.8:1. Of the 81 patients, 32 (39%), 21 (26%), and 28 (35%) had T1-T2, T3, and T4 (TNM International Union Against Cancer staging system, 1997), respectively. Ninety-one percent presented with nodal metastasis. Thirty patients (37%) had lymph nodes >6 cm, and 45 (56%) had bilateral nodes at presentation. Histologically, 77 patients (95%) had undifferentiated carcinoma. Eighty-five percent received neoadjuvant multiagent chemotherapy containing bleomycin, methotrexate, and cisplatin, followed by radiotherapy (RT). RESULTS: After a median follow-up of 50 months, the disease-free survival (DFS) and overall survival (OS) rate for the entire group was 45% and 54%, respectively. Kaplan-Meier curves were used for evaluation of prognostic factors and were compared using the log-rank test. Nodal status had a significant impact on DFS (p = 0.021) and OS (p = 0.006). Complete responders to chemotherapy had superior DFS (p = 0.000) and OS (p = 0.000). RT doses >60 Gy resulted in better DFS (p = 0.020) and OS (p = 0.012). Combined chemotherapy plus RT resulted in improved DFS (p = 0.457) and OS (p = 0.296), although the difference was not statistically significant. CONCLUSION: Combined modality management using chemotherapy and RT resulted in satisfactory locoregional control and OS in pediatric patients with nasopharyngeal carcinoma. Nodal involvement, response to chemotherapy, and RT dose were important prognostic factors.

Stereotactic conformal radiotherapy for posterior fossa tumours: a modelling study for potential improvement in therapeutic ratio.

PURPOSE: To investigate the optimal technique of stereotactic conformal radiotherapy (SCRT) for posterior fossa tumours. MATERIAL AND METHODS: SCRT planning image data sets of four patients with posterior fossa tumours constituted the study material. Based on the operative notes and preoperative imaging, a clinical target volume (CTV) was drawn for each patient. An additional CTV representative of a typical posterior fossa tumour was also drawn on each patient's localisation scans. Therefore a total of eight CTVs differing in their size and location were used for further work. A margin of 5 mm was grown in three dimensions to result in a final planning target volume (PTV). Beam arrangements studied were conformal bilateral parallel pair, a three-field coplanar arrangement with two bilateral and a vertex beam, two three-field non-coplanar techniques and a six-field non-coplanar technique with conformation achieved by micromultileaf collimator (mMLC). Normal structures contoured included normal posterior fossa brain (excluding PTV), brain stem, cochleae, optic apparatus, pituitary-hypothalamic axis (PHA), supratentorial brain and the temporal lobes. Comparative evaluation of plans was done with dose volume histograms (DVH), conformity index (CI) and dose heterogeneity (DH). RESULTS: In all plans, the 95% isodose line covered at least 99% of the PTV with acceptable dose heterogeneity. As compared to the baseline bilateral conformal parallel pair plan, all other plans achieved significantly more sparing of the normal posterior fossa brain at the 95 and 80% dose prescription levels with superior CI (at 95% isodose). The six-field technique resulted in maximum sparing as compared to the bilateral plan with a mean additional sparing of 74% (46.2 cm3) and 55% (33.83) at 95 and 80% dose prescription level, respectively (P<0.0001). Among the three field plans, the technique of bilateral and vertex fields resulted in least doses to cochlea and also irradiated the least volume of brain stem and PHA. Comparison of this technique to the six-field technique did not show any significant difference in sparing of normal structures in the posteriorly placed tumours. In anteriorly placed tumours, the six-field technique was the most optimal irrespective of the size of the target volumes. CONCLUSIONS: A six-field plan SCRT achieves the most significant sparing of the normal tissues for localised irradiation in posterior fossa tumours, particularly for anteriorly located tumours. A relatively simpler three-field plan with bilateral and a vertex beam is equally good for tumours that are placed posteriorly and away from the brain stem.

Radiotherapy with or without mitomycin c in the treatment of locally advanced head and neck cancer: results of the IAEA multicentre randomised trial.

BACKGROUND AND PURPOSE: Single agent mitomycin c (MMC) has been shown to improve the outcome of radiotherapy in single institution trials. In order to confirm these findings in a broader worldwide setting, the International Atomic Energy Agency (IAEA) initiated a multicentre trial randomising between radiotherapy alone versus radiotherapy plus MMC. MATERIAL AND METHODS: Patients with advanced head and neck cancer were treated with primary curative radiotherapy (66 Gy in 33 fractions with five fractions per week) +/-a single injection (15 mg/m(2)) of MMC at the end of the first week of radiotherapy. Stratification parameters were tumour localization, T-stage, N-stage, and institution. A total of 558 patients were recruited in the trial from February 1996 to December 1999. Insufficient accrual and reporting led to the exclusion of three centres. The final study population consisted of 478 patients from seven centres. Patients had stage III (n=223) or stage IV (n=255) squamous cell carcinoma of the oral cavity (n=230), oropharynx (n=140), hypopharynx (n=65) or larynx (n=43). Prognostic factors like age, gender, site, size, differentiation and stage were well balanced between the two arms. RESULTS: The haematological side effects of MMC were very modest (<5% grade 3-4) and did not require any specific interventions. Furthermore, MMC did not enhance the incidence or severity of acute and late radiation side effects. Confluent mucositis and dry skin desquamation was common, occurring in 56% and 62% of patients, respectively. The overall 3-year primary locoregional tumour control, disease-specific and overall survival rates were 19, 36 and 30%, respectively. Gender, haemoglobin drop, tumour site, tumour and nodal stage were significant parameters for loco-regional tumour control. There was no significant effect of MMC on locoregional control or survival, except for the 161 N0 patients, where MMC resulted in a better loco-regional control (3-year estimate 16% vs. 29%, P=0.01). CONCLUSIONS: The study did not show any major influence of MMC on loco-regional tumour control, survival or morbidity after primary radiotherapy in stage III-IV head and neck cancer except in N0 patients where loco-regional control was significantly improved.

Prospective assessment of patterns of failure after high-precision definitive (chemo)radiation in head-and-neck squamous cell carcinoma.

PURPOSE: To prospectively analyze patterns of failure in patients with head-and-neck squamous cell carcinoma treated with definitive high-precision radiotherapy with a focus on location of failure relative to target volume coverage. METHODS AND MATERIALS: Sixty patients treated with three-dimensional conformal radiotherapy or intensity-modulated radiation therapy were included. Locoregional failure volume was defined on the planning data set at relapse, and dose received was analyzed by use of dose-volume histograms. RESULTS: Thirteen patients were deemed to have had locoregional failures, of which two did not have any viable tumor on salvage neck dissection, leaving eleven patients with proven persistent or recurrent locoregional disease. Of these, 9 patients had in-field failure, 1 marginal failure, and 1 both in-field and marginal failures. Overall, only 2 of 11 patients (18%) with relapse had any marginal failure. Of the 20 sites of locoregional failure, 15 (75%) were in-field and 5 (25%) marginal. Distant metastases were detected in 3 patients, whereas a second new primary developed in 3 others. With a median follow-up of 26 months (interquartile range, 18-31 months) for surviving patients, the 3-year local control, locoregional control, disease-free survival, and overall survival rates were 75.3%, 74%, 67.2%, and 60.5%, respectively. CONCLUSIONS: Locoregional relapse remains the predominant pattern of failure in head-and-neck squamous cell carcinoma treated with high-precision definitive radiotherapy with the majority of failures occurring "in-field" within the high-dose volume. Marginal failures can occur, particularly in the vicinity of the spared parotid gland. The therapeutic index of high-precision conformal radiotherapy is largely dependent on adequate selection and delineation of target volumes and organs at risk.

Diagnostic performance of response assessment FDG-PET/CT in patients with head and neck squamous cell carcinoma treated with high-precision definitive (chemo)radiation.

PURPOSE: To prospectively assess diagnostic performance of response assessment fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in patients with HNSCC treated with high-precision definitive (chemo)radiation. METHODS: Fifty-seven patients treated on a prospective clinical trial having post-treatment response assessment FDG-PET/CT scans were included. Clinico-pathologic findings and follow-up information was considered as reference standard. RESULTS: First response assessment FDG-PET/CT was done at a median of 9 weeks (inter-quartile range 8-10 weeks) from completion of treatment. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of first response assessment FDG-PET/CT for identifying residual disease at primary site was 50%, 91.8%, 50%, 91.8%, and 86%. The corresponding figures for the neck were 62.5%, 98%, 83.3%, 94.1%, and 93%. With a median follow-up of 26 months (range 7-45 months), the 3-year loco-regional control (83.9% vs 58.3%, p=0.001) and overall survival (68.8% vs 58.3%, p=0.063) was significantly better in patients with negative response assessment scans. CONCLUSION: The overall diagnostic accuracy of response assessment FDG-PET/CT is good, but its sensitivity and PPV is somewhat low, particularly for primary site. A negative response assessment FDG-PET/CT scan is highly suggestive of absence of viable disease that could be used to guide decision-making.

Prevalence of tobacco use and tobacco-dependent cancers in males in the Rural Cancer Registry population at Barshi, India.

BACKGROUND: In the Rural Cancer Registry at Barshi (western Maharashtra, India), it has been found that the incidence of cancer is relatively low. AIM: To explain the low incidence of tobacco related cancers in males on the basis of prevalence of their tobacco habits. SETTING AND DESIGN: Simple random sample of villages from Barshi Rural Cancer Registry. MATERIAL AND METHODS: A tobacco survey was carried out in 5,319 adult males. Site specific incidence data for Barshi and Mumbai Cancer Registries were available from published reports in the National Cancer Registry Programme. Published report of prevalence of tobacco habits in Mumbai males was available. RESULTS: The tobacco survey showed that the prevalence of smoking compared to Mumbai was low (9.9% vs 23.6%) and the incidence of smoking dependent cancers viz., cancers of oropharynx, larynx and lung were significantly low (P< 0.05). However, although the proportion of tobacco chewers is higher in Barshi compared to Mumbai, the incidence rates for cancer of hypopharynx and oral cancer which are predominantly chewing dependent did not show higher rate than in Mumbai. CONCLUSIONS: The low incidence of smoking dependent cancers in males can be explained by the low prevalence of smoking habit but further studies are needed to explain the observed incidence of predominantly chewing dependent cancers.

Radical radiotherapy with concurrent weekly cisplatin in loco-regionally advanced squamous cell carcinoma of the head and neck: a single-institution experience.

BACKGROUND: The dominant pattern of failure for squamous cell carcinoma of head and neck remains loco-regional, although distant metastases are now being increasingly documented. Radical radiotherapy with concurrent chemotherapy is contemporary standard of care in the non-surgical management of these loco-regionally advanced cancers, based on large randomized controlled trials utilizing high-dose cisplatin (80-100 mg/m2) cycled every three-weekly during definitive radiotherapy. Although efficacious, this is associated with high acute morbidity necessitating intensive supportive care with attendant resource implications. The aim of this retrospective study was to assess the efficacy and acute toxicity of an alternative schedule i.e. concurrent weekly cisplatin-based radical radiotherapy and it's potential to be an optimal regimen in advanced head and neck cancers. METHODS: Outcome data of patients with Stage III & IV head and neck squamous cell carcinoma, excluding nasopharynx, planned for radical radiotherapy (66-70 Gy) with concurrent weekly cisplatin (30 mg/m2) treated in a single unit between 1996-2004 was extracted. RESULTS: The dataset consisted of 264 patients with a median age of 54 years. The median radiotherapy dose was 70 Gy (range 7.2-72 Gy) and median number of chemotherapy cycles was 6 (range 1-7). Two-thirds (65%) of patients received > or = 85% of planned cisplatin dose. With a mean follow-up of 19 months, the 5-year local control; loco-regional control; and disease free survival was 57%; 46%; and 43% respectively. Acute grade 3 or worse mucositis and dermatitis was seen in 77 (29%) and 92 (35%) patients respectively, essentially in patients receiving doses > or = 66 Gy and 6 or more cycles of chemotherapy. Other toxicities (hematologic, nausea and vomiting) were mild and self-limiting. Overall, the acute toxicity of this concurrent weekly chemo-radiation regimen though mildly increased did not mandate intensive supportive care. Stage grouping, primary site, and intensity of treatment were significant predictors of loco-regional control and disease free survival. CONCLUSION: Radical radiotherapy with concurrent weekly cisplatin has moderate efficacy and acceptable acute toxicity with potential to be an optimal regimen in loco-regionally advanced squamous cell carcinoma of the head and neck, particularly in limited-resource settings. Stage grouping, primary site, and treatment intensity are important determinants of outcome.