Efficacy and safety of EGFR inhibitor gefitinib in recurrent or metastatic cervical cancer: a preliminary report.

There has been growing interest in the use of epidermal growth factor receptor inhibitors in various cancers. The study was conducted to evaluate the efficacy and safety of gefitinib as a monotherapy in patients with recurrent or metastatic cervical cancer. Patients with cervical carcinoma who experienced locoregional recurrence or distant metastases either at presentation or after definitive combined chemoradiotherapy or postoperative radiotherapy were enrolled. Gefitinib was administered orally at a dose of 250 mg/d to eligible patients. Treatment with Gefitinib was continued until disease progression, intolerable adverse effects were developed, or consent was withdrawn. Clinical and radiological investigations were used to verify the disease response. Toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The study enrolled 32 patients who met the eligibility criteria. Thirty patients were available for the analysis. The majority of the patients included in the analysis had FIGO stage IIIB disease at their initial presentation. The median follow-up time was 6 months (3-15 months). Two patients (7%) had a complete clinical response, 7 patients (23%) had a partial response, 5 patients (17%) showed a stable disease and 16 patients had progressive disease (53%). The disease control rate was 47%. The median PFS was noted to be 4.5 months and the 1-year PFS was 20%. None of the individuals experienced toxicity of grade 3 or higher. All toxicities were managed conservatively. The study suggests that gefitinib may be a promising therapeutic option for patients with advanced cervical cancer who have limited treatment alternatives.

Geographic and demographic distribution and access to brachytherapy in India with its implications on cancer care.

PURPOSE: Geographic access to medical care varies for nearly every specialty in India. Given the special nature of its treatments, which sometimes necessitate numerous visits over a lengthy period, and the substantial-high fixed cost infrastructure requirements for radiation facilities, radiation oncology is particularly prone to regional inequities in access to care. Brachytherapy (BT) is emblematic of several of these access difficulties since it necessitates specialized equipment, the capacity to maintain a radioactive source, and particular skill sets. The study was conducted to report the availability of BT treatment units in relation to state-level population, overall cancer incidence, and gynecologic cancer incidence. METHODS AND MATERIALS: The availability of BT resources at the state level in India was and the population of each state was estimated using data from the Government of India's Census. The number of cancer cases was approximated for each state and union territory. The total number of gynecological cancers that required BT was determined. The BT infrastructure was also compared to those of other nations in terms of the number of BT units available per million people and for various malignancies. RESULTS: A heterogeneous geographic distribution of BT units was noted across India. India has one BT unit for every 42,93,031 population. The maximum deficit was seen in Uttar Pradesh, Bihar, Rajasthan, and Odisha. Among the states having BT units, the maximum units per 10,000 cancer patients was noted in Delhi (7), Maharashtra (5) and Tamil Nadu (4) and the least was noted in the Northeastern states (<1), Jharkhand, Odisha, and Uttar Pradesh. In BT of gynecological malignancies alone an infrastructural deficit ranging from 1 to 75 units were noted across the states. It was noted that only 104 out of the 613 medical colleges in India had BT facilities. On comparing the BT infrastructure status with other countries India had one BT machine for every 4,181 cancer patients when compared to United States (1 every 2,956 patients), Germany (2,754 patients), Japan (4,303 patients), Africa (10,564) and Brazil (4,555 patients). CONCLUSION: The study identified the deficits of BT facilities in terms of geographic and demographic aspects. This research provides a roadmap for the development of BT infrastructure in India.

Dosimetric Study to Estimate Deviations in Delivered Radiation Dose due to Occluded Air Spaces in Vaginal Vault Brachytherapy Applications.

BACKGROUND: To develop a dosimetric tool to estimate the dose delivered in the presence of air pockets with EBT3 film while simulating the conditions of vaginal vault brachytherapy (VVBT) with 3.0 diameter cylindrical applicator at a prescription dose distance of 5mm from the surface of it. MATERIALS AND METHOD: Six acrylic plates (10 cm x 10 cm, 0.5 cm thick) with four different types of slots were designed and produced locally. They can hold a cylindrical vaginal brachytherapy applicator in the centre, air equivalent material from the applicator's surface [(sizes 4.5 mm (A), 3.0 mm (B), and 2.0 mm (C)], EBT3 film at the prescribed dose distance, and holder rods. Plates were layered together with acrylic rods and assembled in a holding box in a water phantom. Three treatment plans done in TPS with prescription doses of 2 Gy, 3 Gy, and 4 Gy at 5.0 mm with a treatment length of 6 cm, and were executed in Co-60-based HDR brachytherapy unit (M/s SagiNova, Germany) with & without the placement of air equivalent material, and the dose received at slot locations A, B, & C were noted. RESULTS: The mean percentage deviation of measured dose without and with presence of air pocket at A, B and C was 13.9%, 11.0% and 6.4% respectively for all dose prescriptions. As the air pocket size expanded radially from 2.0 mm to 4.5 mm, the increase in dosage ranged from 6.4% to 13.9% which was due to the fact that the film was held at dosage prescription distance and the lack of attenuation of photons radially through air pocket. CONCLUSIONS: The present study can be carried out with a 3D printed phantom that simulates VVBT application having air pockets of different dimensions at different locations and also can be analyzed with Monte Carlo simulations.

Comparison of two high dose rate intracavitary brachytherapy regimens in treatment of cervical cancer: a preliminary report.

BACKGROUND: To assess and compare the local control and toxicities between HDR Intracavitary Brachytherapy with 7.5 Gy and 9 Gy per fraction after EBRT in treatment of carcinoma cervix. METHODOLOGY: A total of 180 patients were randomly assigned to 2 arms. Arm A received HDR intracavitary brachytherapy with a dose of 7.5 Gy per fraction, 1 fraction per week for 3 fractions and Arm B received 9 Gy per fraction, 1 fraction per week for 2 fractions. Patients were evaluated on follow up for assessment of local control and toxicities. RESULTS: The median follow up was 12 months (6-18 months). In arm A 89% of the patient had complete response and 11% had recurrence or metastasis. In arm B 93% of the patient had complete response and 7% had recurrence or metastasis. Grade 2/3 diarrhoea was seen in 4.4% of patients in Arm A and in 7.7% in Arm B. Grade 2/3 proctitis was seen in 3.3% of patients in 7.5 Gy arm and in 6.6% in 9 Gy arm. One patient in each arm had grade 1 haematuria. The overall duration of treatment was significant lower in Arm B compared to Arm A (59 days vs 68 days, p = 0.01). CONCLUSION: The result of this clinical study shows that Intracavitary brachytherapy with a dose of 9 Gy per fraction is non inferior to other schedules in term of local control and does not result in increased toxicity.

In-vivo Comparison of Planned and Measured Rectal Doses during Cobalt-60 HDR CT-based Intracavitary Brachytherapy Applications of Cervical Cancer Using the PTW 9112 Semiconductor Probe.

BACKGROUND: A semiconductor rectal probe was used to compare planned and measured rectal doses during Co-60 high dose rate (HDR) CT-based intracavitary brachytherapy applications (ICBT) of cervical cancer. MATERIALS AND METHODS: A total of 22 HDR brachytherapy applications were included from 11 patients who were first treated with EBRT to the whole pelvis with a total prescribed dose of 50 Gy in 25 fractions. During each application, a PTW 9112 probe rectal probe having a series of five semiconductor diodes (R1 to R5) was inserted into the patient's rectum and a CT-based HDR ICBT application with a prescribed dose per fraction of 7 or 7.5 Gy to HRCTV was performed. Measurements were carried in water phantom using PTW rectal and universal adaptor plugs. Doses measured in phantom and with patients were compared to those calculated by the treatment planning system. RESULTS: The mean percentage dose difference ΔD (%) between calculated and measured values from phantom study were -5.29%, 1.89%, -2.72%, -4.76, and 0.72% for R1, R2, R3, R4, and R3 diodes, respectively and the overall mean ΔD (%) value with standard deviation (SD) was -2.03%±9.6%. From the patient study, a ΔD (%) that ranged from -19.5% to 24.0%, which corresponded to dose disparities between -0.77 Gy and 0.66 Gy. The median ΔD (%) ranged from 0.4% to 1.3%, or -0.03 to 0.05 Gy, respectively. ΔD (%) values exceeded 10% in approximately 26.4% of measurements (29 out of 110 in 22 applications). The location of Rmax in computed and measured values differs in 5 of 22 applications might be due to possible displacement of rectal probe between simulation and treatment. CONCLUSION: Despite the likely geometrical shift of measuring detectors between insertion and treatment, in-vivo dosimetry is feasible and can be used to estimate the dose to the rectum during HDR ICBT.

Evaluation of Inhomogeneity Correction Performed by Radiotherapy Treatment Planning System.

BACKGROUND: Aim of this study is to evaluate the efficacy of inhomogeneity corrections calculated by radiotherapy treatment planning system (TPS) using various densities of materials. MATERIALS AND METHODS: Gammex Computed tomography electron density inserts (EDI's; 14 no's) were used to generate the CT to ED curve with high speed GE CT scanner by noting down the respective HU values of each rod. Treatment plans were generated in XiO TPS with three inhomogeneous phantoms (comprising combination of water, lung and bone equivalent slabs) with different field sizes and for EDI (8 no's) inserted in slots of acrylic tray and validation was carried out using 2D array detector with 20cm×20cm field size for 200 MU. Point dose and fluence measurements were carried with inhomogeneous phantoms combinations and EDI's (placed on the locally fabricated box filled with water medium). RESULTS: The mean percentage deviations with standard deviation of calculated point doses against measured ones obtained with 2D array detector at iso-center plane for all three inhomogeneous phantom combinations were found to be -1.13%±0.13%, -3.51%±0.14% and -0.63%±0.27% respectively. On point doses measured under each individual EDI, over all percentage deviation with standard deviation observed is -2.04% ± 1.1%. CONCLUSION: The described method can be implemented in any newly established radiotherapy department as a routine quality measure of TPS to verify its efficacy in performing of inhomogeneity calculation.

Fabrication and development of a thorax phantom to evaluate 3D CRT treatment planning techniques for post-mastectomy chest wall radiotherapy.

The aim of this study was to design and fabricate a thorax phantom to quantify the radiation doses to the region of the chest wall (with 3 ionization chambers), the organ at risk (OAR) (lung), and the surface using radiochromic films (EBT3) for three different 3D CRT treatment planning techniques. Anthropomorphic phantoms are one of the best tools for verifying the quality of the radiotherapy treatment plans generated by treatment planning systems since they can provide equivalent human tissue densities. Thirty acrylic plates were cut into ellipses 21 cm in height and 31 cm in width, and slots were created to insert lung equivalent cork material and bone equivalent Teflon material. Three treatment planning techniques were designed: (A) tangential pair beams, (B) tangential pair beams with wedges and (C) tangential beams followed by an anterior oblique beam. The percentage difference between the measured point doses and the calculated doses (measured with three CC13 ionization chambers) ranged from - 3.2 to 1.6%, with a mean deviation of - 1.04 ± 1.3%. The measured mean percentage doses on the target surface with EBT3 film were 90.3% and 95.1% of the prescribed dose with 5-mm and 10-mm boluses, respectively. Finally, the average absolute dose difference between the measured and calculated surface doses was within 10 cGy in all three planning techniques. The developed thorax phantom is suitable for point dose measurements using ionization chambers and for surface dose measurements using EBT3 Gafchromic films in post-mastectomy chest wall radiotherapy.

Surface Dose Measurements in Chest Wall Postmastectomy Radiotherapy to Achieve Optimal Dose Delivery with 6 MV Photon Beam.

Aim: A tissue-equivalent bolus of sufficient thickness is used to overcome build up effect to the chest wall region of postmastectomy radiotherapy (PMRT) patients with tangential technique till Radiation Therapy Oncology Group (RTOG) Grade 2 (dry desquamation) skin reaction is observed. The aim of this study is to optimize surface dose delivered to chest wall in three-dimensional radiotherapy using EBT3 film. Materials and Methods: Measurements were conducted with calibrated EBT3 films with thorax phantom under "open beam, Superflab gel (0.5 cm) and brass bolus conditions to check correlation against TPS planned doses. Eighty-two patients who received 50 Gy in 25# were randomly assigned to Group A (Superflab 0.5 cm gel bolus for first 15 fractions followed by no bolus in remaining 10 fractions), Group B or Group C (Superflab 0.5 cm gel or single layer brass bolus, respectively, till reaching RTOG Grade 2 skin toxicity). Results: Phantom measured and TPS calculated surface doses were within - 5.5%, 4.7%, and 8.6% under open beam, 0.5 cm gel, and single layer of brass bolus applications, respectively. The overall surface doses (OSD) were 80.1% ±2.9% (n = 28), 92.6% ±4.6% (n = 28), and 87.4% ±4.7% (n = 26) in Group A, B, and C, respectively. At the end of treatment, 7 out of 28; 13 out of 28; and 9 out of 26 patients developed Grade 2 skin toxicity having the OSD value of 83.0% ±1.6% (n = 7); 93.7% ±3.2% (n = 13); and 89.9% ±5.6% (n = 9) in Groups A, B, and C, respectively. At the 20th-23rd fraction, 2 out of 7; 6 out of 13; and 4 out of 9 patients in Groups A, B, and C developed a Grade 2 skin toxicity, while the remaining patients in each group developed at the end of treatment. Conclusions: Our objective to estimate the occurrence of optimal dose limit for bolus applications in PMRT could be achieved using clinical EBT3 film dosimetry. This study ensured correct dose to scar area to protect cosmetic effects. This may also serve as quality assurance on optimal dose delivery for expected local control in these patients.

Simultaneous Measurement of In vivo and Transit Mid-Plane Doses with Ionization Chambers in Gynecological Malignancy Patients Undergoing Three-Dimensional Conformal Radiotherapy.

PURPOSE: The aim of this study is to estimate delivered radiation doses inside planning tumor volume (PTV) using the in vivo (mid-plane dose) measurement and transit measurement methods in gynecological malignancy patients undergoing three-dimensional conformal radiotherapy (3DCRT) using calibrated ionization chambers. MATERIALS AND METHODS: Six patients with histopathologically proven carcinoma of the cervix or endometrium were planned with four-field 3DCRT to the pelvic site. Isocenter was at the geometric mid-plane of PTV with a dose prescription of 50 Gy in 25 fractions. Clinical mid-plane dose (D iso, Transit) estimates were done in one method (transit) using the FC-65 positioned at electronic portal imaging device level. In another method, a repeat computerized tomography scan was performed (at the 11th fraction) using CC-13 having a protective cap in the vaginal cavity for in vivo measurements (D in vivo ). Simultaneous measurements were performed with the two chambers from the 11th fraction onward at least 3-4 times during the remaining course of treatment. RESULTS: The agreement of mean doses from these two described methods and treatment planning system reference doses was in the range of -4.4 ± 1.1% (minimum) to -0.3 ± 2.0% (maximum) and -4.0 ± 1.7% (minimum) to 1.9 ± 2.4% for D in vivo and D iso, Transit , respectively, which are an acceptable range of daily radiation dose delivery. CONCLUSION: The fundamental importance of this study lies in simultaneous validation of delivered dose in real time with two methods. A study in this small number of patients has given the confidence to apply transit measurements for quality assurance on a routine basis as an accepted clinical dosimetry for the selected patients.

Influence of Air Gap under Bolus in the Dosimetry of a Clinical 6 MV Photon Beam.

AIM: In some situations of radiotherapy treatments requiring application of tissue-equivalent bolus material (e.g., gel bolus), due to material's rigid/semi-rigid nature, undesirable air gaps may occur beneath it because of irregularity of body surface. The purpose of this study was to evaluate the dosimetric parameters such as surface dose (Ds), depth of dose maximum (dmax), and depth dose along central axis derived from the percentage depth dose (PDD) curve of a 6 MV clinical photon beam in the presence of air gaps between the gel bolus and the treatment surface. MATERIALS AND METHODS: A bolus holder was designed to hold the gel bolus sheet to create an air gap between the bolus and the radiation field analyzer's (RFA-300) water surface. PDD curves were taken for field sizes of 5 cm × 5 cm, 10 cm × 10 cm, 15 cm × 15 cm, 20 cm × 20 cm, and 25 cm × 25 cm, with different thicknesses of gel bolus (0.5, 1.0, and 1.5 cm) and air gap (from 0.0 to 3.0 cm), using a compact ionization chamber (CC13) with RFA-300 keeping 100 cm source-to-surface (water) distance. The dosimetric parameters, for example, "Ds," "dmax," and difference of PDD (maximum air gap vs. nil air gap), were analyzed from the obtained PDD curves. RESULTS: Compared to ideal conditions of full contact of bolus with water surface, it has been found that there is a reduction in "Ds" ranging from 14.8% to 3.2%, 14.9% to 1.1%, and 12.6% to 0.7% with the increase of field size for 0.5, 1.0, and 1.5 cm thickness of gel boluses, respectively, for maximum air gap. The "dmax" shows a trend of moving away from the treatment surface, and the maximum shift was observed for smaller field size with thicker bolus and greater air gap. The effect of air gap on PDD is minimal (≤1%) beyond 0.4 cm depth for all bolus thicknesses and field sizes except for 5 cm × 5 cm with 1.5 cm bolus thickness. CONCLUSIONS: The measured data can be used to predict the probable effect on therapeutic outcome due to the presence of inevitable air gaps between the bolus and the treatment surface.

Clinical implementation of brass mesh bolus for chest wall postmastectomy radiotherapy and film dosimetry for surface dose estimates.

OBJECTIVE: This study presents the dosimetric data taken with radiochromic EBT3 film with brass mesh bolus using solid water and semi-breast phantoms, and its clinical implementation to analyze the surface dose estimates to the chest wall in postmastectomy radiotherapy (PMRT) patients. MATERIALS AND METHODS: Water-equivalent thickness of brass bolus was estimated with solid water phantom under 6 megavoltage photon beam. Following measurements with film were taken with no bolus, 1, 2, and 3 layers of brass bolus: (a) surface doses on solid water phantom with normal incidence and on curved surface of a locally fabricated cylindrical semi-breast phantom for tangential field irradiation, (b) depth doses (in solid phantom), and (c) surface dose measurements around the scar area in six patients undergoing PMRT with prescribed dose of 50 Gy in 25 fractions. RESULTS: Water-equivalent thickness (per layer) of brass bolus 2.09 ± 0.13 mm was calculated. Surface dose measured by film under the bolus with solid water phantom increased from 25.2% ±0.9% without bolus to 62.5% ± 3.1%, 80.1% ± 1.5%, and 104.4% ± 1.7% with 1, 2, and 3 layers of bolus, respectively. Corresponding observations with semi-breast phantom were 32.6% ± 5.3% without bolus to 96.7% ± 9.1%, 107.3% ± 9.0%, and 110.2% ± 8.7%, respectively. A film measurement shows that the dose at depths of 3, 5, and 10 cm is nearly same with or without brass bolus and the percentage difference is <1.5% at these depths. Mean surface doses from 6 patients treated with brass bolus ranged from 79.5% to 84.9%. The bolus application was discontinued between 18th and 23rd fractions on the development of Grade 2 skin toxicity for different patients. The total skin dose to chest wall for a patient was 3699 cGy from overall treatment with and without bolus. CONCLUSIONS: Brass mesh bolus does not significantly change dose at depths, and the surface dose is increased. This may be used as a substitute for tissue-equivalent bolus to improve surface conformity in PMRT.

Correlaçäo entre eletrocardiograma de esforço e cineangiocoronariografia / The correlation between exercise electrocardiography and coronary angiography

Levantaram-se os resultados dos 2.800 testes de esforço realizados no Hospital Gastroclínica de Säo Paulo, no período compreendido entre fevereiro de 1973 e agosto de 1982, e encontraram-se 411 casos considerados positivos dos quais 77 foram encaminhados à cineangiocoronariografia. Buscou-se, com este trabalho, estabelecer uma correlaçäo entre as alteraçöes vistas ao ECG de esforço e as encontradas na cineangiocoronariografia. Os achados obtidos na amostra enfatizam a importância do teste de esforço dada a sensibilidade encontrada. No sexo masculino foi encontrada freqüência de ateromatose muito maior em relaçäo ao sexo feminino, no qual se notou uma alta freqüência de falso-positivos. Observou-se ainda a importância do prolapso de válvula mitral, tornando positivo o teste de esforço

Forma variante da síndrome da cimitarra / Variant form of scimitar syndrome

Estuda-se a síndrome da cimitarra e suas variantes através de revisäo da literatura e relato de um caso raro com sinal da cimitarra (forma variante). Dentro da liteatura levantada näo foi encontrado caso contendo todas as características apresentadas em relaçäo a esta forma variante