Shaleen Kumar

Variations of intracavitary applicator geometry during multiple HDR brachytherapy insertions in carcinoma cervix and its influence on reporting as per ICRU report 38

PURPOSE This paper examines the extent of variation in the applicator geometry during multiple high dose rate (HDR) intracavitary brachytherapy (ICBT) applications and its impact on reporting as per ICRU report 38. MATERIALS AND METHODS Eighty orthogonal radiographs from 20 consecutive patients of carcinoma cervix (FIGO stages, IIA-IIIB) having four HDR ICBT applications of 6 Gy each at weekly intervals following teletherapy were evaluated. The applicator consisted of a flexible intrauterine tandem (IUT) independent of the ovoid assembly. The applicator geometry was evaluated in terms of: alpha angle, beta angle, intrauterine length (IUTL), interovoid (IOV), os to right ovoid (ORT) and os to left ovoid (OLT) distances along with vertical (VDL) and anteroposterior displacements (ADL) of the os with respect to the ovoids. The Cartesian co-ordinates (X, Y, and Z) of the IUT tip, centre of both ovoids and os were also measured. Doses to right point A (ARD), left point A (ALD), along with a reference volume of 6 Gy for ICRU height (IRH), width (IRW), thickness (IRT) and volume (IRV) were estimated for each application. RESULTS Highly significant differences (P<0.001) between four insertions in any given patient across 20 patients for alpha angle, beta angle, IUTL, IOV, ORT, VDL, co-ordinates of the IUT, ovoids and os were observed, except for ADL (P=0.041) and OLT (P=0.247). As a consequence, variations were observed in ARD (P=0.027), ALD (P=0.017); IRH, IRW, IRT and IRV (all P<0.001). Applicator factors which influenced the various dose specification parameters were: beta angle and ORT for both ARD and ALD; UTLN, VDL and ORT for IRH; UTLN and IOV for IRW; UTLN for IRT and VDL for the 6 Gy IRV. CONCLUSIONS A significant variation of the applicator geometry and its movement was observed in patients undergoing multiple HDR ICBT. This could have implications for reporting dose and volume specifications as required by ICRU report 38.

Role of GSTM3 Polymorphism in the Risk of Developing Esophageal Cancer

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

Cranial nerve palsy in multiple myeloma and solitary plasmacytoma

Cranial nerve involvement in multiple myeloma and solitary plasmacytoma is rare. We report on two patients who developed cranial nerve palsy due to skull base plasmacytoma. Patient 1, a 55‐year old man with multiple myeloma, developed right sixth cranial nerve palsy during a phase of chemotherapy. He had an intracranial plasmacytoma in the clival region and was treated with 30 Gy whole brain radiotherapy. Patient 2, a 40‐year old man, presented with right third cranial nerve palsy and was detected to have a solitary skull base plasmacytoma. He was treated with radiotherapy followed by thalidomide plus dexamethasone.

Interaction of EGFR 497Arg>Lys With EGF 61A>G Polymorphism: Modulation of Risk in Esophageal Cancer

Genetic polymorphisms in EGFR 497Arg>Lys and EGF +61A>G genes influence cell cycle progression, apoptosis, angiogenesis, and metastasis. Therefore, we assessed association of esophageal cancer (EC), its clinical characteristics, and environmental interactions with these polymorphisms in 174 patients with EC and 196 controls. No association of EGFR 497Arg/Arg genotype was observed (OR 1.48, p = 0.067) but EGF +61A/A genotype was significantly associated with risk of EC (OR 1.65, p = 0.025), particularly in males (OR 1.76, p = 0.031). Patients with EGF +61A/A genotype were at risk for squamous cell carcinoma (SCC) (OR 1.70, p = 0.021) and tumor at upper anatomical location (OR 3.11, p = 0.009). Interaction of EGF or EGFR genotypes with environmental exposure did not modulate EC risk. However, in gene-gene interaction, EGFR 497Arg/Arg*EGF +61A/A showed significant risk for EC (OR 2.47, p = 0.011). In conclusion, EGF +61A>G gene polymorphisms influenced EC susceptibility and its clinical characteristics. Gene-gene interaction of EGFR 497Arg>Lys and EGF +61A>G polymorphisms enhanced risk for EC, indicating additive effects.

Performance evaluation of respiratory motion‐synchronized dynamic IMRT delivery

The purpose of this study was to evaluate the capabilities of DMLC to deliver the respiratory motion‐synchronized dynamic IMRT (MS‐IMRT) treatments under various dose rates. In order to create MS‐IMRT plans, the DMLC leaf motions in dynamic IMRT plans of eight lung patients were synchronized with the respiratory motion of breathing period 4 sec and amplitude 2 cm (peak to peak) using an in‐house developed leaf position modification program. The MS‐IMRT plans were generated for the dose rates of 100 MU/min, 400 MU/min, and 600 MU/min. All the MS‐IMRT plans were delivered in a medical linear accelerator, and the fluences were measured using a 2D ion chamber array, placed over a moving platform. The accuracy of MS‐IMRT deliveries was evaluated with respect to static deliveries (no compensation for target motion) using gamma test. In addition, the fluences of gated delivery of 30% duty cycle and non‐MS‐IMRT deliveries were also measured and compared with static deliveries. The MS‐IMRT was better in terms of dosimetric accuracy, compared to gated and non‐MS‐IMRT deliveries. The dosimetric accuracy was observed to be significantly better for 100 MU/min MS‐IMRT. However, the use of high‐dose rate in a MS‐IMRT delivery introduced dose‐rate modulation/beam hold‐offs that affected the synchronization between the DMLC leaf motion and target motion. This resulted in more dose deviations in MS‐IMRT deliveries at the dose rate of 600 MU/min. PACS numbers: 87.53.kn, 87.56.N‐

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

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

Dosimetric effect of multileaf collimator leaf width in intensity-modulated radiotherapy delivery techniques for small- and large-volume targets

The purpose of this study was to evaluate the dosimetric effect of the leaf width of a multileaf collimator (MLC) in intensity-modulated radiotherapy (IMRT) delivery techniques for small- and large-volume targets. We retrospectively selected previously treated 5 intracranial and 5 head-neck patients for this study to represent small- (range, 18.37-72.75 cc; mean, 42.99 cc) and large-volume (range, 312.31-472.84 cc; mean, 361.14 cc) targets. A 6-MV photon beam data was configured for Brianlab m3 (3 mm), Varian Millennium 120 (5 mm) and Millennium 80 (10 mm) MLCs in the Eclipse treatment-planning system. Sliding window and step-shoot IMRT plans were generated for intracranial patients using all the above-mentioned MLCs; but due to the field size limitation of Brainlab MLC, we used only 5-mm and 10-mm MLCs in the head-and-neck patients. Target conformity, dose to the critical organs and dose to normal tissues were recorded and evaluated. Although the 3-mm MLC resulted in better target conformity (mean difference of 7.7% over 5-mm MLC and 12.7% over 10-mm MLC) over other MLCs for small-volume targets, it increased the total monitor units of the plans. No appreciable differences in terms of target conformity, organ at risk and normal-tissue sparing were observed between the 5-mm and 10-mm MLCs for large-volume targets. The effect of MLC leaf width was not quantifiably different in sliding window and step and shoot techniques. In addition, we observed that there was no additional benefit to the sliding-window (SW) technique when compared to the step-shoot (SS) technique as a result of reduction of MLC leaf width.

Dosimetric verification of gated delivery of electron beams using a 2D ion chamber array.

The purpose of this study was to compare the dosimetric characteristics; such as beam output, symmetry and flatness between gated and non-gated electron beams. Dosimetric verification of gated delivery was carried for all electron beams available on Varian CL 2100CD medical linear accelerator. Measurements were conducted for three dose rates (100 MU/min, 300 MU/min and 600 MU/min) and two respiratory motions (breathing period of 4s and 8s). Real-time position management (RPM) system was used for the gated deliveries. Flatness and symmetry values were measured using Imatrixx 2D ion chamber array device and the beam output was measured using plane parallel ion chamber. These detector systems were placed over QUASAR motion platform which was programmed to simulate the respiratory motion of target. The dosimetric characteristics of gated deliveries were compared with non-gated deliveries. The flatness and symmetry of all the evaluated electron energies did not differ by more than 0.7 % with respect to corresponding non-gated deliveries. The beam output variation of gated electron beam was less than 0.6 % for all electron energies except for 16 MeV (1.4 %). Based on the results of this study, it can be concluded that Varian CL2100 CD is well suitable for gated delivery of non-dynamic electron beams.

Investigation of Inter and Intra-fractional Uncertainties in Lung IMRT delivery

Changes in the tumour position due to inter and intra-fractional motion introduce uncertainty in IMRT delivery. In this work, we experimentally evaluated the effect of inter and intra-fractional motion uncertainties in the IMRT delivery. A lung patient was planned with five field dynamic IMRT for a total dose of 60Gy in 30 fractions using 6MV photon beam at a dose rate of 400MU/min. The plan was delivered on Varian CL2100CD Linear Accelerator with millennium 120 MLC for a single fraction and measured using IMRT MatriXX placed on Quasar motion platform, aligned with respect to isocentre for planar as well as point dose measurements. This measurement was summated for thirty fractions and taken as reference. Thirty measurements were performed for each inter-fractional, intra-fractional and combined effect. The setup errors (Mean±SD) used to simulate the inter-fractional displacements were RL: -0.10±0.27mm, SI: 0.17±0.45mm, AP: -0.04±0.38mm and Rot: 0.02±0.86 degree. The intra-fractional motion was simulated using the motion platform parallel to the MLC leaf motion, for amplitude of 1cm and period of 4s. The planner fluence of inter, intra-fractional motion and combination of both was analyzed against the reference using gamma criteria of 3%/3mm. Similarly the point dose measurements were also compared. The maximum deviation in point dose during a single fraction was -3.8%, 3.1% and -5.9% for interfractional, intra-fractional and combined respectively. The same resulted in deviation of -0.4%, -0.3% and 0.1% respectively when summated for 30 fractions. The percentage of pixels failing the gamma criteria during a single fraction was 28.0%, 16.4% and 28.5% for inter-fractional, intra-fractional and combined respectively. The same revealed 11.4%, 12.4% and 19.2% respectively when summated. Though the point dose deviations were nullified over thirty fractions, the planner fluence variation was observed to be considerable.

Synchronization of Intra-fractional Motion in Dynamic IMRT Delivery

One of the limitations of breath-hold and gated treatments is the prolongation of treatment time. Hence, it is noteworthy to incorporate the intra-fractional motion into the IMRT delivery without holding or gating the beam. The purpose of this study was to develop a method for synchronization of intra-fractional motion in dynamic IMRT delivery. An in-house program was developed in MATLABTM. A dynamic MLC (DMLC) file was imported into the program from the Eclipse treatment planning system (TPS). The program modifies the DMLC file by incorporating the target motion. In this study, target motion was assumed to have amplitude of 2cm and period of 4s. The modified DMLC file was sent for delivery to the linear accelerator (CL2100CD) equipped with millennium 120 MLC. Dosimetric measurements were carried out using IMRT MatriXX 2D array device which was placed over the QUASAR motion platform. In order to evaluate the accuracy of synchronization of intra-fractional motion in delivery (SIMD), the fluence of TPS DMLC file was measured using static detector (no motion). The IMRT MatriXX was moved in cranio/caudal direction (parallel to MLC leaf motion) for the above assumed target motion. The fluence of SIMD was measured for this moving detector using the modified DMLC file. Further, in order to show the benefit of SIMD, the fluence of non-SIMD was also measured, using the original TPS DMLC file which was delivered to the moving detector. The gamma evaluation criterion of 3% / 3mm was used to compare the SIMD and non-SIMD with static delivery. The percentage of pixels passing the criteria in gamma evaluation was 94.4% for SIMD and 63.17% for non-SIMD. This demonstrates that SIMD was able to compensate the intra-fractional motion and could deliver the fluence similar to static.