Systematic overview of preoperative chemoradiation trials in esophageal cancer: in response to article by Ian Geh et al.
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Antineoplastic Agents↗
Biomedical subjects
K A Dinshaw
Publications and source records attributed to K A Dinshaw.
Altered fractionated radiotherapy in head and neck cancer.
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Age Factors↗
Split therapy: planned neck dissection followed by definitive radiotherapy for a T1, T2 pharyngolaryngeal primary cancer with operable N2, N3 nodal metastases--a prospective study.
BACKGROUND: The management of patients with a small pharyngolaryngeal cancer (T1 and T2) with large nodal metastases is a subject of debate. We present data on the feasibility and outcome of treating these patients with surgery for the nodal metastases followed by definitive radiotherapy. METHODS: Prospective study of 59 patients of small pharyngolaryngeal primary squamous carcinomas with operable (N2/N3) nodal metastasis treated with neck dissection followed by radiotherapy. RESULTS: Complete nodal clearance was achieved in 54 (90%). The mean nodal size was 4 cm and extranodal extension was seen in 88% of patients in the study group. There were no significant postoperative complications. Median interval between surgery and radiotherapy was 23 days. Forty-nine patients (83%) started their RT within 6 weeks of surgery. With a median follow-up of 25 months, the disease free and overall survival was 54% and 60% (5 years). CONCLUSION: The management of patients with a radiocurable pharyngolaryngeal primary with large nodes by this approach is a feasible option with adequate control and survival.
Adult↗
Radical radiotherapy in head and neck squamous cell carcinoma: an analysis of prognostic and therapeutic factors.
AIMS: Head and neck squamous cell carcinoma (HNSCC) continues to be a leading cancer in developing countries. Definitive radiation therapy either primary or as postoperative adjuvant is offered to most patients. We aimed to identify prognostic and therapeutic factors that affect locoregional control and survival in patients undergoing radical radiotherapy for head and neck squamous cell cancers. MATERIALS AND METHODS: A retrospective analysis of 568 previously untreated patients with squamous head and neck cancers, who received radical radiotherapy between 1990 and 1996, using local control, locoregional control and disease-free survival (DFS) as outcome measures. RESULTS: With a median follow-up of 18 months for living patients, the 5-year local control, locoregional control and DFS for all 568 patients were 53%, 45% and 41%, respectively, for all stages combined. The 5-year local control, locoregional control and DFS as per the American Joint Committee on Cancer stage grouping were 78%, 70% and 70%; 64%, 59% and 57%; 51%, 42% and 37%; and 40%, 27% and 22% from stages I to IV, respectively, with highly significant P values. Patients receiving higher doses (> or = 66 Gy) had a significantly better outcome compared with lower doses. The 5-year local control (59% vs 48%, P = 0.0015), locoregional control (47% vs 41%; P = 0.0043) and DFS (44% vs 37%; P = 0.0099) were significantly better in patients receiving > or = 66 Gy. Site of primary also affected outcome significantly, with oral cavity lesions faring badly. CONCLUSION: Tumour stage remains the most important factor affecting outcome in radical radiotherapy of HNSCC. A definite dose-response relationship exists with higher total doses, leading to better local control, locoregional control and DFS in all stages. Site of primary affects outcome too, with laryngeal primaries doing well and oral cavity cancers faring the worst.
Adult↗
Peripheral dose from uniform dynamic multileaf collimation fields: implications for sliding window intensity-modulated radiotherapy.
The increase in the number of monitor units in sliding window intensity-modulated radiotherapy, compared with conventional techniques for the same target dose, may lead to an increase in peripheral dose (PD). PD from a linear accelerator was measured for 6 MV X-ray using 0.6 cm3 ionization chamber inserted at 5 cm depth into a 35 cm x 35 cm x 105 cm plastic water phantom. Measurements were made for field sizes of 6 cm x 6 cm, 10 cm x 10 cm and 14 cm x 14 cm, shaped in both static and dynamic multileaf collimation (DMLC) mode, employing strip fields of fixed width 0.5 cm, 1.0 cm, 1.5 cm, and 2.0 cm, respectively. The effect of collimator rotation and depth of measurement on peripheral dose was investigated for 10 cm x 10 cm field. Dynamic fields require 2 to 14 times the number of monitor units than does a static open field for the same dose at the isocentre, depending on strip field width and field size. Peripheral dose resulting from dynamic fields manifests two distinct regions showing a crest and trough within 30 cm from the field edge and a steady exponential fall beyond 30 cm. All dynamic fields were found to deliver a higher PD compared with the corresponding static open fields, being highest for smallest strip field width and largest field size; also, the percentage increase observed was highest at the largest out-of-field distance. For 6 cm x 6 cm field, dynamic fields with 0.5 cm and 2 cm strip field width deliver PDs 8 and 2 times higher than that of the static open field. The corresponding factors for 14 cm x 14 cm field were 15 and 6, respectively. The factors by which PD for DMLC fields increase, relative to jaws-shaped static fields for out-of-field distance beyond 30 cm, are almost the same as the corresponding increases in the number of monitor units. Reductions of 20% and 40% in PD were observed when the measurements were done at a depth of 10 cm and 15 cm, respectively. When the multileaf collimator executes in-plane (collimator 90 degrees) motion, peripheral dose decreases by as much as a factor of 3 compared with cross-plane data. The knowledge of PD from DMLC field is necessary to estimate the increase in whole-body dose and the likelihood of radiation induced secondary malignancy.
Humans↗
Breast movement during normal and deep breathing, respiratory training and set up errors: implications for external beam partial breast irradiation.
This study was designed to evaluate interfraction and intrafraction breast movement and to study the effect of respiratory training on respiratory indices. Five patients were immobilized in supine position in a vacuum bag and three-dimensional set up errors, respiratory movement of the breast during normal and deep breathing, tidal volume and breath hold time were recorded. All patients underwent respiratory training and all the respiratory indices were re-evaluated at the end of training. Cumulative maximum movement error (CMME) was calculated by adding directional maximum set up error and maximum post training movement during normal breathing. The mean set up deviation was 1.3 mm (SD +/- 0.5 mm), 1.3 mm (SD +/- 0.3 mm) and 4.4 mm (SD +/- 2.6 mm) in the mediolateral, superoinferior and anteroposterior dimensions. Pre-training mean of the maximum marker movement during normal breathing was 1.07 mm, 1.94 mm and 1.86 mm in the mediolateral, superoinferior and anteroposterior dimensions. During deep breathing these values were 2 mm, 5.5 mm and 4.8 mm. While respiratory training had negligible effect on breast movement during normal breathing, it resulted in a modest reduction during deep breathing (p = 0.2). The mean CMME recorded for these patients was 3.4 mm, 4.5 mm and 7.1 mm in the mediolateral, superoinferior and anteroposterior dimension. Respiratory training also resulted in an increase in breath hold time from a mean of 31 s to 44 s (p = 0.04) and tidal volume from a mean of 560 cm(3) to 1160 cm(3) (p = 0.04). With patients immobilized in the vacuum bag the CMMEs are relatively less. Individualized directional margins may aid in reduction of planning target volume (PTV).
Brachytherapy↗
Radiotherapeutic management of locally advanced head and neck cancer.
Head and neck cancer management has undergone several paradigm shifts for several relevant reasons. From the dismal experience with the use of radiotherapy as the sole modality in the treatment of this group of patients with advanced disease, radiotherapy has been evaluated as an adjuvant for the same group of patients who had undergone successful surgery. Although there is no level 1 evidence to support postoperative adjuvant radiation, several studies have demonstrated that adjuvant radiotherapy reduces the local failures and, thereby, improves survival. Predictors of recurrence after surgical resection are: positive margins of resection; extranodal spread in involved nodes; perineural invasion; and presence of two or more involved regional lymph nodes. Realization of the advantages of a combination of chemotherapy with radiotherapy has had a major impact on the management of these cancers. There is emerging evidence for the use of adjuvant concurrent chemoradiotherapy in the group with high-risk features. Multiple organ conservation strategies in the management of locally advanced head and neck cancers have evolved over the years. However, the meta-analyses of impact of chemotherapy in various settings reveal that concomitant chemoradiotherapy is superior to any of the other regimens. Increasing use of computed tomography, magnetic resonance imaging and positron emission tomography scan images has resulted in better visualization of target volumes and critical structures. Delineation of these structures is of paramount importance and has resulted in a profound change in conformal treatment planning. Better understanding of the physical aspects of delivery of radiotherapy and the advent of modern treatment planning systems have led to the development of conformal techniques. Although the benefit of these techniques on survival have yet to be demonstrated, there is evidence to suggest that they reduce treatment-related toxicities significantly and facilitate dose escalation. Increased knowledge of radiobiology has led to the development of various altered fractionation regimens in the management of locally advanced head and neck cancers. Discovery of cell-cycle kinetics and signal transduction pathways has led to the unearthing of several potential targets for targeted therapy. The epidermal growth factor receptor gene has emerged as the most promising target. The role of biological radiation response modifiers is evolving. All of these approaches to improve the therapeutic gain would be incomplete without evaluating their effect on the quality of life of these patients.
Antineoplastic Combined Chemotherapy Protocols↗
Ultrasonographic changes in malignant neck nodes during radiotherapy in head and neck squamous carcinoma.
Limited information is available about the sonomorphological changes in metastatic neck nodes during radiotherapy. The aim of this study was to evaluate the pattern of sonomorphological changes in metastatic neck nodes with radiotherapy. The study population consisted of 16 consecutive patients planned for radical radiotherapy to the head and neck. All patients were subjected to four ultrasound examinations: before therapy, at 46 Gy, at the conclusion of radiation and at first follow up. A total of 59 ultrasound examinations were performed on 16 patients. The difference between the mean number of nodes detected per patient before (10.6) and after (7.8) radiation was significant (P = 0.05). Sixteen nodes were categorized as malignant at first sonography, half of which reverted back to normal by the end of radiation. Changes in the sonomorphology of malignant cervical lymph nodes occur with radiotherapy with more that half demonstrating reversion to normal pattern. Future studies correlating this with histopathology should be considered.
Aged↗
Consolidation radiation after complete remission in Hodgkin's disease following six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy: is there a need?
PURPOSE: Combined modality treatment using multidrug chemotherapy (CTh) and radiotherapy (RT) is currently considered the standard of care in early stage Hodgkin's disease. Its role in advanced stages, however, continues to be debated. This study was aimed at evaluating the role of consolidation radiation in patients achieving a complete remission after six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy using event-free survival (EFS) and overall survival (OS) as primary end points. PATIENTS AND METHODS: Two hundred and fifty-one patients with Hodgkin's disease attending the lymphoma clinic at the Tata Memorial Hospital (Mumbai, India) from 1993 to 1996 received induction chemotherapy with six cycles of ABVD after initial staging evaluation. A total of 179 of 251 patients (71%) achieved a complete remission after six cycles of ABVD chemotherapy and constituted the randomized population. Patients were randomly assigned to receive either consolidation radiation or no further therapy. RESULTS: With a median follow-up of 63 months, the 8-year EFS and OS in the CTh-alone arm were 76% and 89%, respectively, as compared with 88% and 100% in the CTh+RT arm (P =.01; P =.002). Addition of RT improved EFS and OS in patients with age < 15 years (P =.02; P =.04), B symptoms (P =.03; P =.006), advanced stage (P =.03; P =.006), and bulky disease (P =.04; P =.19). CONCLUSION: Our study suggests that the addition of consolidation radiation helps improve the EFS and OS in patients achieving a complete remission after six cycles of ABVD chemotherapy, particularly in the younger age group and in patients with B symptoms and bulky and advanced disease.
Adolescent↗
Transperineal low-dose rate iridium-192 interstitial brachytherapy in cervical carcinoma stage IIB.
PURPOSE: To assess local control, survival and complications in patients with cervical carcinoma Stage IIB treated radically with transperineal Iridium-192 low-dose rate interstitial brachytherapy following external beam radiotherapy. PATIENTS AND METHODS: 65 women (age 25-70 years, mean 47 years) with cervical carcinoma Stage IIB were initially treated with external beam radiotherapy on a telecobalt or 6 MV linear accelerator to a dose of 50 Gy delivered in 5-6 weeks. After 2-3 weeks of completing external radiation, patients received interstitial brachytherapy with Iridium-192 (activity 0.5-1 mCi/cm) using a Syed-Neblett perineal template. The median dose delivered to the implant volume was 24 Gy (range 20-32 Gy) delivered at an average dose rate of 0.70 Gy/h (range 0.40-1.20 Gy/h). A point defined at 1.5 cm lateral to the central uterine tandem at the level of os was taken as a representative for assessing the dose to the cervix. Mean doses delivered by interstitial brachytherapy to point A, cervix, point B and rectum were 38 Gy, 34 Gy, 16 Gy and 16 Gy, respectively. RESULTS: At a median follow-up of 53 months, the actuarial disease free survival and overall survival for 65 patients at both 5 and 10 years was 64% and 44%, respectively. Response to radiotherapy was a strong predictor of local control with 82% of patients continuing to have pelvic control after initial complete response. Overall, nine (14%) patients had persistent disease, ten (15%) developed a central recurrence after initial control and three patients developed distant metastasis on follow-up. No patient had any immediate treatment-related complication. Late toxicity included grade I-II rectal reactions in five patients and grade IV bladder complication (vesico-vaginal fistula) in two patients. 5 years after treatment, one patient developed intestinal obstruction, which was relieved after conservative management. Two patients developed vaginal stenosis. The 5- and 10-year disease free survival was 48% in patients aged less than 45 years as compared to 80% in patients of more than 45 years (p = 0.009). Dose to the cervical point was a prognostic indicator with 5- and 10-year disease free survival of 47% in patients who received < 35 Gy in comparison to 80% in patients who had > 35 Gy (p = 0.03). There was no difference in local control and survival in patients with minimal and moderate parametrial involvement. Bulky disease (> 4 cm) at presentation and a longer gap between external radiation and brachytherapy showed a trend towards inferior local control. CONCLUSIONS: Interstitial brachytherapy after external beam irradiation in patients with cervical carcinoma Stage IIB results in acceptable local control, survival and complication rates. Increased dose to the cervical disease results in improved local control and survival and should therefore be considered while optimizing brachytherapy treatment plans. Comparison of the results with those of standard intracavitary therapy remains to be proven in a randomized trial.
Adenocarcinoma↗
Primary extranodal mucosa associated lymphoid tissue (MALT) lymphoma of the prostate.
Low-grade B-cell mucosa associated lymphoid tissue (MALT) lymphoma can rarely present primarily in extranodal sites other than stomach, which is the most common site for it. Until now only four cases of primary prostatic MALTomas have been described in the literature and we report the fifth. We describe a case of primary prostatic MALToma in a 67-year-old man and the diagnosis was made on the trans-urethral resection specimen of the prostate. As the disease was limited to prostate (stage IEA), the patient was treated with external beam radiation therapy to a total dose of 4400cGy in 22 fractions. The patient achieved completed remission and has remained free of disease in the following 36 months.
Disease-Free Survival↗
Radiation therapy in T1-T2 glottic carcinoma: influence of various treatment parameters on local control/complications.
PURPOSE: To evaluate the influence of various treatment parameters on local control as well as complications in T1 and T2 glottic carcinomas. METHODS AND MATERIALS: Between 1975 and 1989, 676 patients with early glottic carcinoma (460 T1 and 216 T2) received curative radiation with three different treatment regimens, as follows: Regimen 1-50 Gy/15 Fr/3 weeks (3.33 Gy/daily) for 192 patients; Regimen 2-60-62.5 Gy/24-25 Fr/5 weeks (2.5 Gy/daily) for 352 patients; and Regimen 3-55-60 Gy/25-30 Fr/5-6 weeks (2-2.25 Gy/daily) for 132 patients. RESULTS: The local control at 10 years was 82% and 57% for T1 and T2 lesions respectively (p = 0.0). For the T1N0M0 group, field size had significant impact on local control with both univariate (p = 0.05) and multivariate (p = 0.03) analysis. For T2N0M0, group field size (p = 0.03) as well as registration year (p = 0.016) were significant in univariate analysis whereas only field size remained significant on multivariate analysis. Persistent radiation edema was noted in 146 (22%) patients and was significantly worse with larger field size (p = 0.000) but not related to different treatment regimens. CONCLUSION: The shorter fractionation schedule had comparable local control, without increased complications in comparison to the protracted schedule and is best suited for a busy department.
Adult↗
Primary carcinoma of the vagina: Tata Memorial Hospital experience.
PURPOSE: Carcinoma of the vagina is a rare gynecological malignancy comprising approximately 2% of all the gynecological malignancies. We have analyzed the treatment outcome of the patients treated at the Tata Memorial Hospital from January 1984 to December 1993. METHODS AND MATERIALS: In this 10-year period, 134 patients of primary vaginal cancers were registered at our hospital. Of these, 75 patients received complete treatment and are analyzed. RESULTS: Disease-free survival (DFS) for the whole group is 50%, and overall survival (OAS) is 60%. Most locoregional recurrences and distant failures are noted in the 2 years following treatment. DFS at 5 years is as follows: Stage I (5 patients), Stage IIA (37 patients), Stage IIB (15 patients), Stage III (14 patients), and Stage IV (4 patients); are 40%, 55%, 60%, 50%, and 25%, respectively. The DFS for patients with complete response (42 patients) to external radiation at 5 years is 68%, with partial response (25 patients) is 35%, and with poor or no response (6 patients) is 18% (p = 0.0000). We observed that brachytherapy was an important part of the treatment, and patients who received brachytherapy (59 patients), either with a vaginal intracavitary applicator (30 patients) or interstitial implant (29 patients) had a DFS of 53% and 56%, respectively, while 15 patients who received external radiation alone had a DFS of 30%. Patients receiving brachytherapy within 4 weeks of external radiation had a DFS of 60% as compared to 30% when the interval was more than 4 weeks. CONCLUSION: The factors indicating prognosis are: site and extent of involvement, presence of lymph nodes at presentation, technique of brachytherapy, and interval between external radiation and brachytherapy.
Adolescent↗
Epstein-Barr virus association in classical Hodgkin's disease provides survival advantage to patients and correlates with higher expression of proliferation markers in Reed-Sternberg cells.
BACKGROUND: Most Epstein-Barr virus (EBV) associated lymphoproliferative disorders have high proliferation indices. However, classical Hodgkin's disease (cHD) is heterogeneous, with respect to proliferation index of the Reed-Sternberg cell (RS cell), and EBV association. Hence, we investigated whether cHD with and without EBV-association differ with respect to the proliferation index of the RS cells. Further we investigated whether this would have a bearing on patients survival. PATIENTS AND METHODS: We investigated 110 cases of cHD for: a) EBV association by immunohistochemical demonstration of EBV-latent membrane protein-1 and EBV encoded nuclear RNA 1 by mRNA in situ hybridisation; b) Proliferating cell nuclear antigen (PCNA) expression in the RS cells. RESULTS: EBV association was noted in 86 of 110 cases (78%). Higher PCNA expression (P = 0.004) and younger age (P = 0.001) correlated independently with EBV association. The 10 year relapse free survival (RFS) of EBV+ and EBV- patients were 60% and 44%, respectively (P = 0.03). The 10 year overall survival (OS) of EBV+ and EBV- patients were 85% and 64%, respectively (P = 0.03). EBV association maintained its significant impact on RFS and OS within Cox proportional hazard model. CONCLUSIONS: Our study suggests that EBV is likely to confer a higher PCNA expression and also contribute towards maintaining the RS cells of cHD in cell cycle. Hence, RS cells in EBV associated cHD would be more responsive to chemotherapy and radiotherapy associated DNA damage. Thus, EBV-association provides survival advantage to cHD patients treated with standard chemotherapy and radiotherapy protocols.
Adolescent↗
Discrepancies in Epstein-Barr virus association at presentation and relapse of classical Hodgkin's disease: impact on pathogenesis.
BACKGROUND: Though Epstein-Barr virus (EBV) has been linked to classical Hodgkin's disease (cHD), only a proportion of cHD cases show EBV-association. While there has been evidence to suggest a crucial role for EBV in the early phase of cHD evolution, we are unclear whether continued presence of EBV is essential for the maintenance of the neoplasm. We have addressed this issue by investigating the EBV-association in paired samples of cHD obtained at presentation and relapse. MATERIALS AND METHODS: We have analysed lymph node biopsy samples from 23 cases of cHD at presentation and relapse. In situ hybridization with EBER-1 probe and immunostaining with anti latent membrane protein-1 (LMP-1) antibody was performed on the paraffin sections. PCR for EBNA 3C gene was performed for EBV subtype analysis on the DNA extracted from paraffin sections. RESULTS: EBV-association was documented in both the presentation and relapse samples of 14 cases. One case showed loss of EBV-association at relapse. PCR analysable DNA was obtained from both presentation and relapse samples in four of the EBV-associated cases. The EBNA 3C amplimer corresponded to type A strain of EBV in all the samples. CONCLUSION: Loss of EBV-association between presentation and relapse seen in one case implies a hit and run mechanism in EBV-induced lymphomagenesis. Though EBV may be essential early in the evolution of cHD, it may not be required for maintenance of the neoplastic clone. Our study also brings out a speculation that a proportion of EBV-negative cHD could represent loss of EBV in the tumour prior to clinical presentation. Alternatively, an unidentified lymphotropic virus other than EBV might play a pathogenetic role in EBV-negative cHD.
Burkitt Lymphoma↗
The quality of swallowing for patients with operable esophageal carcinoma: a randomized trial comparing surgery with radiotherapy.
BACKGROUND: Surgery is considered the standard treatment for operable esophageal carcinoma, although there is no compelling evidence that surgery can achieve better results than radiotherapy. There has previously been no direct randomized comparison of these two modalities with survival or disease specific outcome end points. METHODS: Ninety-nine patients with operable squamous cell carcinoma of the esophagus were randomly allocated to surgery or radiotherapy after stratification for tumor length (< or = or >5 cm). Those randomized to surgery underwent transthoracic esophagectomy with limited lymphadenectomy, whereas those in the radiotherapy arm received 50 gray in 28 fractions followed by a 15-gray boost to the primary tumor. Disease specific outcome was assessed for 4 subgroups: 1) disease specific symptoms, 2) physical symptoms, 3) ability to work, and 4) social/family interaction and global perception of disease specific outcome. The questionnaire was given prior to treatment and posttreatment at 3-month intervals for 1 year. Death was a secondary end point. RESULTS: There was an overall improvement in the quality of swallowing in both treatment arms after treatment and with the passage of time. The swallowing status was better in the surgery arm than in the radiotherapy arm at 6 months after treatment (P = 0.03, Fisher's exact test). Logistic regression analysis showed randomization arm (P = 0.035), time since treatment (P = 0.003), and pretreatment swallowing status to be significant determinants of posttreatment swallowing status. Surgery was twice as likely to result in improvement in swallowing than radiotherapy after correction for time and pretreatment swallowing status. Overall survival was better in the surgery arm than in the radiotherapy arm (P = 0.002, log rank test) (OR = 2.74 with 95% confidence intervals 1.51-4.98; P < 0.009, Cox proportional hazards model). CONCLUSIONS: Both surgery and radiotherapy can improve the quality of swallowing significantly for patients with operable esophageal carcinoma. Surgery is marginally superior to radiotherapy in improving the quality of swallowing. In this trial, survival in the surgery arm was significantly better than in the radiotherapy arm, although the small number of patients is a limitation.
Carcinoma, Squamous Cell↗
Country profile: India.
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Education, Medical↗
Survival analysis of 5595 head and neck cancers--results of conventional treatment in a high-risk population.
This is a study of 5595 head and neck cancer patients treated during 1987-89 at TMH, Mumbai. The study included 1970 oral cancers (ICD 140-145), 1495 oropharyngeal cancers (ICD 1410, 1453, 146), 1255 hypopharyngeal cancers (ICD 148), 125 nasopharyngeal cancers (ICD 147) and 750 laryngeal cancers (ICD 161). The clinical extent of disease at presentation was based on TNM group staging (UICC 1978). For the majority of sites, patients attended the hospital during stage III and stage IV of the disease; the only exception was for cancers of the lower lip, anterior tongue and vocal cord when between 46.2% and 56.5% of patients with localized cancer (stage I and II) were seen. Generally, surgery either alone or with radiation has been administered for oral cancer patients whereas radiation either alone or in combination with chemotherapy was administered for other head and neck sites. The overall 5-year survival rate was in the range of 20-43% for oral cancer, 8-25% for pharyngeal cancers and 25-62% for laryngeal cancer. The 5-year relative survival rates were more or less in agreement with the results published by the Eurocare study for head and neck cancers. The importance of primary prevention in head and neck cancer is stressed.
Combined Modality Therapy↗