Primary Mediastinal Germ Cell Tumors (PMGCT): A Real-world Analysis From A Tertiary Cancer Care Center in India.

BACKGROUND: Primary mediastinal GCT (PMGCT) is a rare entity and comprises 10-15% of all mediastinal tumors. We present our institutional experience of MGCT treated with multimodality management. MATERIALS AND METHODS: We conducted a retrospective analysis between 2010 to 2020 of all mediastinal germ cell tumors registered at our center. Data on patient demographics, treatments received, treatment toxicities and response were recorded. Overall survival and relapse free survival were estimated using Kaplan-Meier methods. RESULTS: A total of 30 patients were identified. The median age was 25.5 (range, 18-45) years. Common presenting features included cough (70%) and shortness of breath (70%). Histology wise, 60% patients were non seminomatous histology, whereas 33.3% patients were Seminoma. Twenty-seven (90%) patients received chemotherapy as the first-line treatment, of whom five patients (16.6%) underwent surgery and radiation therapy subsequently. Median follow-up was 26.9 months. Thirteen patients (43.3%) had complete response (43.3%) and eight patients had partial response (26.7%), while three patients (5.5%) had progressive disease. Three-year relapse-free survival rate was 69.6% (95% confidence interval [CI], 42.8-85.6%). Overall survival (OS) at 3 years was 73.4% (95% CI, 49.4-87.3%). Patients with seminoma had a 3 year OS of 90.0% (95% CI, 47.3-98.5%) compared to those with non-seminoma (63.53% [95% CI, 32.3-83.3%]). CONCLUSIONS: Multiagent chemotherapy is the backbone of treatment in PMGCT. Seminomatous PMGCT have excellent prognosis, while further improvement is needed in those with nonseminomatous tumor.

Ga-68 PSMA PET/CT in recurrent high-grade gliomas: evaluating PSMA expression in vivo.

PURPOSE: We planned this prospective study to evaluate PSMA expression in recurrent high-grade gliomas (rHGG), including anaplastic astrocytoma and glioblastoma using Glu-NH-CO-NH-Lys-(Ahx)-[Ga-68 (HBED-CC)]- (Ga-68 PSMA) positron emission tomography (PET), with its theranostic potential in mind. METHODS: This was a prospective study enrolling patients with clinical and MRI evidence of rHGG on follow-up. Three treated cases of HGG with RN on MRI were also included as negative controls. Abnormal tracer accumulation in the brain parenchyma, more than the contralateral hemisphere was interpreted as positive study. For semiquantitative analysis, a 3D spherical region of interest (ROI) was drawn around the site of the abnormal Ga-68 PSMA uptake, and the ratio of SUVmax of tumor (T) to SUVmax of the contralateral corresponding area (TBR) was calculated. Each patients' PSMA brain PET was fused to the corresponding MRI and reviewed for concordance. RESULTS: Thirty patients were included in the study, a total of 49 lesions were detected on MRI, and fused PET/MR images showed increased Ga-68 PSMA uptake in all these lesions. Multifocal lesions were better appreciated on fused PET-MR images, and concordance between MRI and PET was 100 % for patient and lesion-wise detection. Recurrent glioma lesions showed SUVmax and SUVmean values (median and IQR) 6.0 (4.4-8.2) and 3.3 (2.8-3.7), respectively. Lesions labeled as radiation necrosis on MRI did not show tracer accumulation. CONCLUSION: Ga-68 PSMA has potential utility for evaluating recurrence in HGG and its potential for theranostics would encourage its use in the evaluation of these patients.

Mission impossible: chemotherapy in the intensive care for pineal region germ cell tumor.

Pineal region tumors are rare and a heterogenous group of primary central nervous system tumors which are primarily classified as germ cell tumors and non-germ cell tumors. Chemotherapy and radiotherapy as the primary treatment modalities have been reported to result in good outcomes. We discuss the case of a young girl who presented to our emergency department in an unconscious state and had a large lesion in the posterior third ventricular region, but without any associated hydrocephalus which could explain her stuporous state. Given the rapid decline in her sensorium, we were faced with the difficult choice between surgical decompression of the tumor and a trial of rescue chemotherapy following histopathological confirmation through biopsy. She underwent an open biopsy followed by chemotherapy in a neurosurgical intensive care unit despite her poor Karnofsky performance score. She improved after chemotherapy and her tumor decreased in size significantly over time. We highlight the role of chemotherapy administered in the neurosurgical ICU to an unconscious patient with a large chemoresponsive tumor leading to rapid shrinkage of the lesion and gradual improvement in the sensorium of the patient.

Hypofractionated radiotherapy with temozolomide in diffuse intrinsic pontine gliomas: a randomized controlled trial.

INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) is the most common form of brainstem glioma. The present study was performed to assess if hypofractionated radiotherapy completed in < 3 weeks with temozolomide improves survival in DIPG. MATERIAL AND METHODS: The present study is a phase II open label randomized trial. The study included newly diagnosed patients with DIPG. Patients in arm A received conventional fractionated RT of 60 Gy in 30 fractions over 6 weeks while patients in arm B received hypo-fractionated radiotherapy of 39 Gy in 13 fractions over 2.6 weeks along with concurrent Temozolomide (TMZ) 75 mg/m2 from day 1 to day 17 followed by adjuvant TMZ for six cycles. The survival analysis was performed with modified intention to treat analysis. RESULTS: A total of 35 patients were randomized. 33 patients were evaluable. 93% (n = 14) of patients in the conventional arm completed treatment while only 17% (n = 3) of the children could complete planned course of treatment in the experimental arm. The median overall survival (OS) was 11 months (95% CI - 7.5 to 14.5 months) in the conventional arm and 12 months (95% CI - 10.5 to 13.5 months) in the experimental arm (p = 0.208). 28% (n = 5) patients in the experimental arm developed grade 3 or 4 hematological toxicity. CONCLUSION: The above study shows that hypofractionated radiotherapy with concurrent and adjuvant temozolomide does not improve OS and has higher hematological toxicity. Conventional radiotherapy remains the standard of care.

Fine-Needle Aspiration Cytology (FNAC) in Breast Cancer: A Reappraisal Based on Retrospective Review of 698 Cases.

BACKGROUND: Core needle biopsy is replacing fine-needle aspiration cytology (FNAC) as the modality of choice for breast cancer diagnosis. This study was carried out to determine the usefulness of FNAC in breast cancer patients in a tertiary care center in North India. METHODS: Case files of patients managed in the breast cancer clinic of a single surgical unit between 1993 and 2014 were reviewed. All patients who underwent FNAC at our institute or had their slides reviewed at our institute were included in the study. Patients operated on outside our center and those with FNAC reports which were not available for review were excluded. Data were entered in Microsoft Excel and analyzed with SPSS version 21. True positives and false negatives for FNAC were noted from which sensitivities and positive predictive values (PPVs) were calculated. RESULTS: FNAC was performed in 698 of 1310 patients. Mean age was 48.3 years. There were 9 (1.3%) male breast cancer patients. 696 (99.7%) patients had a palpable lump with a mean tumor size of 5.3 cm. 54.2% of the patients were clinically node positive. While over 80% of patients were diagnosed on the basis of FNAC before 2000, less than 50% of the patients had an FNAC after 2010. FNAC diagnosed malignancy in 627 patients, while it was inconclusive in 69 and false negative in two patients. No false-positive results were seen. These figures yield an absolute sensitivity of 89.8% and a complete sensitivity of 99.7% for FNAC with a 100% PPV. CONCLUSIONS: FNAC is a reliable tool for diagnosing cancer in suspicious breast lesions with a good sensitivity and PPV in hands of an experienced cytopathologist. Surgical treatment may be safely undertaken based on FNAC particularly in early operable breast cancers suitable for breast conservation.

Extent of surgical resection and adjuvant temozolomide improves survival in pediatric GBM: a single center experience.

BACKGROUND: Pediatric glioblastoma (pGBM) is an uncommon entity. The importance of concurrent and adjuvant temozolomide is not known in this subset of patients. METHODS: We retrospectively analyzed our database between 2000 and 2015. All patients were treated with maximally safe surgical resection. This was followed by a uniform treatment schedule of post-operative radiation with concurrent daily temozolomide at 75 mg/m2. Radiation dose was 60 Gy in 30 fractions planned by 3-dimensional conformal radiotherapy. Concurrent and adjuvant temozolomide was used in all patients treated after 2007. Four weeks later, adjuvant temozolomide was started at 150 mg/m2, day 1 to 5 every 28 days and escalated to 200 mg/m2 from the second cycle onwards if well tolerated. Log-rank test was used to compare survival distribution. The data was analyzed using SPSS (version 16). RESULTS: Fifty-one patients were analyzed. Median age was 14 years (range: 5 to 21 years). Thirty-five males and 16 females were noted. Median symptom duration was 4 months. Twenty-eight patients underwent a gross total resection (GTR) while 17 underwent a subtotal resection; six patients underwent decompression. Thirty-three patients received concurrent chemotherapy while 27 received adjuvant chemotherapy. Median progression-free survival (PFS) was 15.1 months. One- and 3-year PFS was 54.4% and 3-year PFS was 24.6.7%. The median overall survival was 17.4 months. In univariate analysis survival was better for gross total resection (17.4 months vs. 11.5 months; p = 0.037), and significance maintained after multivariate analysis p = 0.026, HR 3.069, 95% CI 1.14-8.23. In univariate analysis, survival was better for patients receiving temozolomide but did not achieve significance. However, in multivariate analysis, use of temozolomide was associated with significantly improved survival p = 0.036, HR 3.315, 95% CI 1.07-10.19. CONCLUSIONS: GTR improves survival significantly in pGBM. Adjuvant temozolomide may improve survival in pGBM.

Orbital medulloepithelioma in an adult patient: Radiation-induced second neoplasia?

Second cancers in survivors of hereditary retinoblastoma occur much more commonly than in the general population. This can be attributed both to the germline mutation of the RB gene and chemoradiation used for treatment of this paediatric cancer. Medulloepithelioma is an uncommon tumor of neuroectodermal origin, seen largely in the paediatric population and rarely reported in adults. Though the incidence of second malignancies is common in retinoblastoma, medulloepithelioma as a second malignancy in retinoblastoma survivors is rare, with only one case reported so far. Herein, we present a case of a 29-year-old patient presenting with medulloepithelioma of the right orbit, arising in the radiation field of previously treated retinoblastoma. This case was also peculiar in that though the origin of tumor was in the eyeball it had a very aggressive clinical course.

Clinical Profile and Predictors of Survival in Carcinoma Penis Patients.

BACKGROUND: Carcinoma penis is a rare neoplasm, and the literature is scarce on long-term survival and its predictors. The aim of the study was to determine the clinical profile and management patterns, identify predictors of survival, and the impact of education and rural/urban dwelling on survival. METHODS: Patients with a histological diagnosis of carcinoma penis from January 2015 to December 2019 were included in the study. Demographics, clinical profile, education status, primary residence address, and outcomes were obtained from the case records. Distance from the treatment centre was obtained from the postal code. The primary objectives were to assess relapse-free survival (RFS) and overall survival (OS). The secondary objectives were to identify the predictors of RFS and OS and to determine the clinical profile and treatment patterns in patients with carcinoma penis in India. Time-to-event was calculated by Kaplan-Meir analysis and survival was compared by the log-rank test. Univariate and multivariable Cox regression analyses were used to find independent predictors of relapse and mortality. Logistic regression analyses to examine the associations of rural residence, education status, and distance from the treatment centre with the relapse adjusting for measured confounding variables. RESULTS: Case records of 102 patients treated during the above period were retrieved. The median age was 55.5 (interquartile range [IQR] 42-65 years). Ulcero-proliferative growth (65%), pain (57%), and dysuria (36%) were the most common presenting features. Clinical examination or imaging revealed inguinal lymphadenopathy in 70.6% of patients, however, only 42% of these lesions were pathologically involved. A total of 58.8% of patients were from rural areas, 46.9% had no formal education, and 50.9% had a primary residence ≥100 km from the hospital. Patients with lower education and rural households had higher TNM stages and nodal involvement. Median RFS and OS were 57.6 months (15.8 months to not reached) and 83.9 months (32.5 months to not reached), respectively. On univariate analysis tumor stage, involvement of lymph nodes, T stage, performance status, and albumin was predictive for relapse and survival. However, on multivariate analysis, the stage remained the only predictor of RFS and nodal involvement, and metastatic disease was a predictor of OS. Education status, rural habitation, and distance from the treatment centre were not predictors for relapse or survival. CONCLUSIONS: Patients with carcinoma have locally advanced disease at presentation. Rural dwellings and lower education were associated with the advanced stage but did not have a significant bearing on the survival outcomes. The stage at diagnosis and nodal involvement is the most important predictor of RFS and OS.

Quality of life assessment in testicular non-seminomatous germ cell tumour survivors.

PURPOSE: Patients with Germ cell tumours (GCT) are at risk of long-term toxicities due to multimodality therapy. It is debatable whether there is an impact on the quality of life(QoL) of GCT survivors. METHODS: A case-control study was conducted at a tertiary care centre in India, using the EORTC QLQ C30 questionnaire, to compare the QoL between GCT survivors(disease free > 2 years) and healthy matched controls. A multivariate regression model was used to identify factors affecting QoL. RESULTS: A total of 55 cases and 100 controls were recruited. Cases had a median age of 32 years (interquartile range, IQR 28-40 years), ECOG PS of 0-1(75%), advanced stage III (58%), chemotherapy (94%) and 66% were > 5 years from diagnosis. The median age of controls: 35 years (IQR 28-43 years). A statistically significant difference was seen for emotional (85.8 ± 14.2 vs 91.7 ± 10.4, p 0.005), social(83.0 ± 22.0 vs 95.2 ± 9.6, p < 0.001) and global scales (80.4 ± 21.1 vs 91.3 ± 9.7, p < 0.001). Cases had more nausea and vomiting(3.3 ± 7.4 vs 1.0 ± 3.9, p 0.015), pain(13.9 ± 13.9 vs 4.8 ± 9.8, p < 0.001), dyspnea(7.9 + 14.3 vs 2.7 ± 9.1, p 0.007), and appetite loss(6.7 ± 14.9 vs 1.9 ± 7.9, p 0.016) and greater financial toxicity(31.5 ± 32.3 vs 9.0 ± 16.3, p < 0.001). Adjusting for age, performance status, BMI, stage, chemotherapy, RPLND, recurrent disease, and time since diagnosis, no predictive variables were significant. CONCLUSION: There is a detrimental impact of history of GCT in long term survivors of GCT.

Rosette Forming Glioneural Tumor Treated with Conformal Radiation.

Rosette forming glioneural tumors (RGNT) are a rare type of low-grade brain tumor included in 2007 in WHO classification. Given the benign nature of the disease, a complete surgical excision has been considered optimum. However, a handful of cases have reported the locally aggressive nature of RGNT. In addition, radiation may also be considered for a tumor located in areas where surgical excision is difficult. We present a similar case, where surgical risk was weighed against resection and we treated the patient with conformal radiation.

Differential effect of body mass index (BMI) on outcomes of patients treated with docetaxel in prostate cancer - An exploratory analysis.

OBJECTIVE: There are contradictory data on differential effect of docetaxel based on BMI in patients with breast and prostate cancer. We performed an exploratory analysis to determine if the benefit of docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC) is modified by BMI. METHODS: We performed a post hoc analysis of the data retrieved from the ENTHUSE M1C study. BMI (kg/m2) was categorized as: 18.5 to <25 as lean; 25 to <30 as overweight; and ≥30 as obese. Cox regression models were constructed to determine the impact of BMI on progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 466 patients were eligible for the current analysis. The median PFS was 7.3, 7.7 and 8.4 months (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.81 to 1.06; P = 0.261) in lean, overweight and obese patients. The median OS was 16.6, 20.1 and 21.4 months (HR, 0.75; 95% CI, 0.63 to 0.89; P = 0.002) for lean, overweight and obese patients. After adjusting for baseline and tumor characteristics, there was no association of BMI with PFS (overweight, HR, 0.89; 95% CI, 0.71 to 1.13; P = 0.353; obese, HR, 0.86; 95% CI, 0.66 to 1.13; P = 0.277) while overweight (HR, 0.68; 95% CI, 0.51 to 0.89; P = 0.006) and obese (HR, 0.59; 95% CI, 0.41 to 0.83; P = 0.003) patients had significantly better OS compared with lean patients. CONCLUSIONS: There was no effect of BMI on PFS in patients with mCRPC receiving docetaxel. Interestingly, overweight and obese patients had a longer OS compared with lean patients, which is in contradiction to a recent study in breast cancer; and warrants further investigation.

Glioblastoma with Primitive Neuroectodermal Component Treated with Adjuvant Radiotherapy and Temozolomide: A Pooled Analysis of 23 Patients.

AIM: Glioblastoma (GBM) is one of the most aggressive neoplasms of the central nervous system with dismal survival. In recent years, different variants of GBM have been described in the literature. GBM with areas of neuroectodermal differentiation (GBM-PNET) is a relatively new entity in GBM. Presence of the neuroectodermal component increases the propensity of systemic dissemination as with other intracranial primitive neuroectodermal tumors (PNET). The optimal treatment for these patients remains a controversy, with authors reporting local radiotherapy to craniospinal irradiation and chemotherapy. We intend to analyze the pattern of care for GBM with neuroectodermal component. MATERIALS AND METHODS: We retrieved data of four patients with GBM-PNET treated in our institute; data were also retrieved from published series to derive treatment and outcome results. RESULTS: In this series, we report the outcome of a series of four patients of GBM-PNET treated with adjuvant radiotherapy and temozolomide. All but one patient underwent gross total resection of the tumor. Adjuvant hypofractionated radiation with concurrent and adjuvant temozolomide was used in all cases. The median follow-up was 12.9 months in the present series. One patient experienced local recurrence 18 months after the treatment. A review of published literature on GBM-PNET was done; studies with details of patient outcome were used for an independent analysis. Twenty-three patients were identified, and the pooled analysis revealed a median progression free and overall survival of 10 and 25, months respectively. Extent of surgery, local radiation vs. craniospinal irradiation, and age at presentation had no impact on the survival. CONCLUSION: GBM PNET is a new entity with only few cases reported so far. Clinical behavior and treatment outcome of these tumors are not different from conventional GBM. However, these patients are at higher risk of CSF dissemination. Hence, an individualized treatment approach is best suited.

Anesthesia concerns in prostate brachytherapy: An institutional experience.

BACKGROUND: Prostate cancer is a common cancer found in men worldwide. Brachytherapy is an established modality used for the treatment of these patients. Although anesthetic management of such patients is challenging but the ideal anesthetic technique has not yet been established. Our study aims to identify the most efficacious anesthetic technique for perioperative management of prostate cancer patients undergoing brachytherapy. METHODS: Retrospective analysis of ten patients who underwent 16 brachytherapy sessions under combined spinal epidural (CSE) anesthesia between April 2016 and December 2016 was done. The data were collected, tabulated using MS Excel, and statistically analyzed with EPI Info 6 and SPSS-16 statistical software (SPSS Inc. Chicago, USA) to draw relative conclusions. RESULTS: The median peak sensory dermatome level achieved was T6 and the median maximum motor block achieved was grade 2. The mean (± standard deviation (SD)) time to sensory regression to T10 (range T5-T8) dermatome was found to be 118.00 ± 47.110 (range = 0-238) minutes. Despite the presence of co-morbidities, minor intraoperative complications were observed only in two patients. The postoperative numerical rating scale (NRS) was less than 4 in all patients during the first 24 hours. None of our patients complained of nausea, vomiting, pruritus and respiratory depression. The mean (± SD) patient satisfaction score was 44.40 ± 0.871 (range : 1-5) at the end of 24 hours. CONCLUSIONS: CSE anesthesia is a safe and effective technique for anesthetic management of patients undergoing prostate brachytherapy.

An audit of over 1000 breast cancer patients from a tertiary care center of Northern India.

BACKGROUND: Breast cancer is the commonest cancer among women. India along with United States and China collectively account for one third of the global burden. The present study reports the clinico-epidemiological data of our patient population. This may help in better understanding of the disease in our population and also form ground for conducting further breast cancer research in India. METHODS: The study was conducted at an apex teaching and medical research institution in India from September 2013 to April 2015 as a retrospective review of prospectively collected data of breast cancer patients. The socio-demographic characteristics, reproductive risk factors, clinical presentation, TNM staging and histopathological characteristics for breast cancer in these patients were recorded. The data was recorded on an Xcel spreadsheet and analyzed using IBM SPSS 21. RESULTS: The study comprised of 1310 breast cancer patients with males comprising 1.1%. The median age of presentation was 47 years, and menarche 14 years. Most of women were married and multiparous. More than half of the women were postmenopausal at presentation. All patients were symptomatic at presentation with median duration of symptom of 5 months and median lump size of 5 cm. Most common stage at presentation was Stage II and most common histopathology was Invasive ductal carcinoma. 61.9% tumors were hormone receptor positive. Triple negative cancers formed one third of all tumors. CONCLUSION: Breast cancer in the Indian scenario is a disease of younger woman who lack the characteristic reproductive and demographic risk factors. This calls for a need to study the clinico-demographic risk factors and characteristics of our own population.

177Lu-/68Ga-PSMA Theranostics in Recurrent Glioblastoma Multiforme: Proof of Concept.

A 37-year-old man, treated case of left temporal glioblastoma presented with headache, seizures, and progressive right-sided weakness with MRI evidence of recurrence. Exploratory Ga-PSMA PET/CT demonstrated PSMA expression in the recurrent lesion; it was decided to treat this patient with Lu-PSMA-617. After 3 cycles of Lu-PSMA-617, Ga-PSMA PET/CT showed significant reduction in PSMA uptake and regression in size of lesion on MRI with improvement in patient's symptoms and performance status. Lu-/Ga-PSMA theranostics has potential in patients with recurrent glioblastoma multiforme when other therapeutic options are not feasible.

A rare case of paraganglioma of the sella with bone metastases.

Sellar paragangliomas are very rare lesions with only 11 previous cases described in the literature. We present a further case of sellar paraganglioma. The patient is a 17-year-old man who developed headache, visual blurring, and diplopia. MRI showed a sellar lesion. Trans-nasal trans-sphenoid biopsy showed features of paraganglioma. He was treated by Stereotactic radiotherapy. Four months after treatment he developed bone metastases which was palliated by radiation, zoledronic acid, and chemotherapy. This is the first case of sellar paraganglioma showing metastases to bone.

Osseous Hodgkin's lymphoma-review of literature and report of an unusual case presenting as a large ulcerofungating sternal mass.

Osseous involvement in Hodgkin's lymphoma is uncommon. The most common location is vertebral, primarily in the thoracolumbar region, followed by pelvis, ribs, femur, sternum, clavicle and skull in decreasing incidence. We herein illustrate the salient features of the disease citing a case of a disseminated Hodgkin's lymphoma presenting as a large ulcerofungating sternal mass mimicking chronic tubercular osteomyelitis. The case report highlights the importance of clinical suspicion of unusual presentation of lymphohematopoietic tumors of the bone especially in developing countries, where chronic granulomatous disease is preponderant.

Giant cell glioblastoma with spinal and spinal leptomeningeal metastasis in a child: A rare presentation of a rare tumor.

Giant cell glioblastoma (GCG) is a rare subtype of classic glioblastoma multiforme with favorable prognosis and little is known about its metastatic potential. We hereby present a unique case of GCG in a 7-year-old child who developed spinal and spinal leptomeningeal metastasis during adjuvant therapy. She succumbed to it in spite of salvage therapy.

A study on contralateral breast surface dose for various tangential field techniques and the impact of set-up error on this dose.

The risk of inducing contralateral breast (CLB) cancer in patients undergoing tangential field irradiation for the treatment of breast cancer is a serious concern in radiation oncology. A bilateral breast phantom made of wax attached onto the Alderson Rando phantom was used for studying the CLB dose for techniques using physical wedges, EDWs, IMRT and open fields. The skin dose to the CLB was measured at four different points (3 cm from the medial border of the tangential field (P1), nipple (P3), axilla (P4), midpoint between P3 and P1 (P2)). The highest measured dose occurred at P1 with the 60 degrees physical wedges; it was 15.3% of the dose at isocentre. Similarly, the dose measured at P3 (nipple) with 60 degrees physical wedges was 1.90 times higher than the dose with 60 degrees EDWs. The dose at P1 for IMRT (7.8%) was almost the same as that for the open field (8.7%). The skin dose measured at the nipple was 2.1 - 10.9 % of the isocentre dose. The highest CLB doses were contributed by medial wedged fields. The dose to the CLB can be reduced by using IMRT or avoiding wedging the medial tangential fields. A set-up error in the longitudinal direction has little impact on the CLB dose. Set-up errors > 1 cm in the vertical and lateral directions have significant impact on the CLB dose.