Intra-operative interstitial brachytherapy in a novel infra-zygomatic approach for partially resectable head and neck cancers around the base of skull: A technical note.

Purpose: To report an intra-operative catheter insertion technique into the base of skull tumor bed following surgical resection for maxillary tumors. Material and methods: A 42-year-old male patient diagnosed with carcinoma of the maxilla was treated with neoadjuvant chemotherapy followed by chemo-radiation using external beam technique combined with brachytherapy boost to post-operative bed. Brachytherapy was delivered via intra-operative catheter placement at the base of skull to residual disease, which was surgically unresectable. Initially, catheters were placed cranio-caudally. This was later changed into an infra-zygomatic approach to improve planning and dose coverage. High-risk clinical tumor volume (CTV) was generated with a 3 mm margin to residual gross tumor. Planning was done using Varian Eclipse brachytherapy planning system, and an optimal plan was generated. Conclusions: An innovative, beneficial, and safe brachytherapy approach is necessary in a difficult and critical area, such as the base of skull. Our novel method of implant insertion through infra-zygomatic approach resulted in a safe and successful procedure.

Comparison of dosimetric analysis of organs at risk and target volumes for ovoids and cylinders in endometrial carcinoma.

Purpose: To compare dose volume parameters of target and organs at risk in vaginal vault brachytherapy using ovoids or cylinder in post-operative endometrial carcinoma. Material and methods: The study was done among 25 histologically proven post-operative endometrial carcinoma patients requiring vaginal brachytherapy. All patients underwent both cylinder and ovoids application alternatively on weekly basis. Ovoids size ranged from 2 to 3 cm diameter. Diameters of cylinder ranged between 2.5 and 3.5 cm. Bladder, rectum, urethra, and clinical target volume (CTV) were contoured on CT simulation images. Prescribed dose was 6-7 Gy in 2-3 fractions at 0.5 cm from the surface of applicator. Results: The mean values of D90, D50, V150, V100, V90, and V50 of CTV were comparable between cylinder and ovoids plans. The mean dose of CTV was significantly higher with cylinder than with ovoids, and D100 was significantly higher with ovoids (mean = 15.63 Gy vs. 14.64 Gy, p = 0.016, and D100 = 37.82% vs. 42.86%, p = 0.042, for cylinder vs. ovoids). In the dosimetry of the vault, D90, D50, V100, V90, V50, and mean of the vault did not show any significant difference between cylinder and ovoids. The V150 was significantly higher with cylinder plans than ovoids, and D100 of the vault was significantly higher with ovoids plans (V150 = 14.81% vs. 6.86%, p = 0.02, and D100 = 37.77% vs. 44.80%, p = 0.029, for cylinder vs. ovoids). D0.1cc, D1cc, D2cc, and mean for the bladder, rectum, and urethra were comparable between the cylinder and ovoid plans. Conclusions: The present study showed that the dose to organs at risk, most of the dosimetric parameters of CTV, and vault were comparable between the cylinder and ovoid plans. Both applicators provide good reproducibility. The choice of applicator will ultimately depend on the institutional policies and oncologist decision. However, in patients with dog-ear configuration of the vagina, ovoids may be preferred as per ABS guidelines.

Clinical profile and outcomes in cervical cancer: An audit from a tertiary cancer center.

Background: Carcinoma cervix contributes to a major proportion of cancer treatment in tertiary oncology centers. The outcomes are dependent on multiple factors. We conducted an audit to establish the pattern of treatment practiced for carcinoma cervix at the institute and suggest changes thereof to improve the quality of care. Methodology: A retrospective observational study of 306 diagnosed cases of carcinoma cervix was carried out for the year 2010. Data was collected with regards to diagnosis, treatment, and follow-up. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) version 20. Results: Out of 306 cases, 102 (33.33%) patients received only radiation therapy and 204 (66.66%) patients received concurrent chemotherapy. The most common chemotherapy used was weekly cisplatin 99 (48.52%), followed by weekly carboplatin 60 (29.41%) and three weekly cisplatin 45 (22.05%). Disease-free survival (DFS) at 5 years was 36.6% with patients of overall treatment time (OTT) of <8 weeks and >8 weeks showing DFS of 41.8% and 34% (P = 0.149), respectively. Overall survival (OS) was 34%. Concurrent chemoradiation improved overall survival by a median of 8 months (P = 0.035). There was a trend towards improved survival with three weekly cisplatin regimen, however, insignificant. Stage correlated with improved overall survival significantly with stage I and II showing 40% and stage III and IV showing 32% (P < 0.05) OS. Acute toxicity (grade I-III) was higher in the concurrent chemoradiation group (P < 0.05). Conclusion: This audit was a first of its kind in the institute and threw light on the treatment and survival trends. It also revealed the number of patients lost to follow-up and prompted us to review the reasons for it. It has laid the foundation for future audits and recognized the importance of electronic medical records in the maintenance of data.

Estimation of dose-volume parameters of female urethra as organ-at-risk during interstitial brachytherapy in gynecological malignancies.

PURPOSE: Interstitial brachytherapy (ISBT) is often used as post-external beam radiotherapy (EBRT) to treat locally advanced gynecological malignancies. Female urethra is in close proximity to the target during ISBT. However, it has not been evaluated as an organ-at-risk (OAR). Overlapping symptoms caused by radiation-induced bladder toxicity vs. urethral toxicity make it difficult to identify and report urethral toxicities separately. This was a retrospective study to estimate dose-volume parameters of female urethra during high-dose-rate ISBT. MATERIAL AND METHODS: Data of 24 patients with gynecological malignancies treated by ISBT were selected. Urethra and periurethral regions were retrospectively contoured. Mean volume, Dmax, Dmean, D2cc, D1cc, D0.5cc, D0.2cc, and D0.1cc were documented. Unpaired t-test was used for comparison of means. RESULTS: 20/24 Ca. cervix, 1/24 Ca. vagina, and 3/24 Ca. vaginal vault received 6-6.5 Gy in 4 ISBT fractions. Mean urethral length was 3.54 ±0.55 cm. Mean doses received by urethra per BT fraction were Dmax = 4.23 ±1.32 Gy, Dmean = 2.71 ±1.01 Gy, D0.2cc = 3.31 ±1.07, and D0.1cc = 3.54 ±1.09 Gy. Comparison of total BT 2 Gy equivalent dose (EQD2) with 4 fractions for urethra between patients with (9/24) and without anterior vaginal wall (15/24) involvement included Dmean = 18.79 ±7.49 Gy vs. 11.14 ±6.15 Gy*, D1cc = 10.90 ±10.03 Gy vs. 4.54 ±3.93 Gy*, D0.5cc = 19.50 ±8.69 Gy vs. 11.97 ±6.54 Gy*, D0.2cc = 23.78 ±8.94 Gy vs. 15.51 ±7.39 Gy*, and D0.1cc = 25.88 ±9.37 Gy vs. 17.39 ±8.03 Gy*, respectively (*p < 0.05). CONCLUSIONS: Female urethra receives significant doses during ISBT for gynecological malignancies, especially when the anterior vaginal wall is within the target volume. Reporting doses to urethra would enable to develop clinical correlation and dose-volume constraints for urethra as organ-at-risk in future.

Prostate permanent implant brachytherapy with BARC I-125 Ocu-Prosta seeds.

AIM: The aim of this study is implementation and establishment of standard operating procedure for permanent prostate implant brachytherapy technique using BARC I-125 Ocu-Prosta seeds. MATERIALS AND METHODS: The transrectal ultrasound (US)-guided procedure was used for permanent implant procedure. The Best® Sonalis™ US Imaging System and Best NOMOS™ Treatment Planning system was used for volume study and implant procedure. The BARC provided I-125 Ocu-Pro radioactive seeds were implanted into the patient with help of Mick@ Applicator. The implant was performed based on pre-implant dosimetry and intraoperative planning performed during implant procedure. RESULTS: The necessary quality assurance tests were performed for US system before clinical use. The boost dose of 110 Gy was prescribed to the prostate volume of 34.71 cc. About 48 seeds with activity of 0.35 mCi (each) implanted into the prostate volume with reference to intraoperative planning. At the end of procedure, the patient underwent abdomen fluoroscopic examination, to ensure the seed counts in the prostate volume. The day after the implant, the patient was discharged. One month later a planning computed tomography and treatment planning was performed for seed position and dose verification. CONCLUSIONS: Low dose rate permanent implant brachytherapy has the advantage of being a one-time procedure and the existing long term follow-up supports its excellent outcome and low morbidity. BARC-BRIT is supplying the loose 125I seeds. These seeds can be easily implanted into the patient using Mick applicator. However, the pre-implant seed preparation and implant procedure may result some radiation exposure to staff involved. The radiation dose can be minimized with good practice. This report is one patient pilot study and intended to test the implant systems and standard operative procedure henceforth for permanent implant brachytherapy procedure.

Evaluation of dosimetric impact of inter-application and intra-application variations in fractionated high-dose-rate intra-cavitary brachytherapy of cervical cancer.

PURPOSE: To evaluate feasibility and safety of execution of optimized intra-cavitary brachytherapy (ICBT) plan of first fraction in subsequent fractions in high-volume, low-resource centers. MATERIAL AND METHODS: This non-randomized prospective study included 30 cervical cancer patients, who underwent 4 fractions of high-dose-rate (HDR)-ICBT in 2 applications, one week apart, 2 fractions per application delivered on two consecutive days. Computed tomography (CT) simulation was done before each fraction, organs at risk (OARs) were contoured on all sets of CT images. Optimized plans were generated for each set of CT images and executed for the treatment. Test treatment plans were retrospectively generated by applying first treatment fraction's dwell times adjusted for decay, and dwell positions of the applicator for subsequent treatment fractions paired t-test was performed to analyze D2cc dose variations of OARs among the paired sets of plans. RESULTS: Comparison between the plans showed daily plans provided lower D2cc to OARs than test plans. In intra-application plan comparison, there was a significant dose reduction to 2 cc sigmoid (p = 0.021) and bladder (p = 0.007) in daily plan. Mean D2cc of optimized and unoptimized plans were 361.35 ±114.01 and 411.70 ±152.73 for sigmoid, and 511.23 ±85.47 cGy and 553.57 ±111.23 cGy for bladder, respectively. In inter-application, D2cc rectum and sigmoid demonstrated a statistically significant dose variation (p = 0.002) and (p = 0.007), with mean D2cc rectum of optimized and unoptimized plans being 401.06 ±83.53 cGy and 452.46 ±123.97 cGy, and of 2 cc sigmoid 340.84 ±117.90 cGy and 387.79 ±141.36 cGy, respectively. CONCLUSIONS: Fractionated HDR brachytherapy amounts to significant variation in OAR doses if re-simulation and re-plan is not performed for every fraction and ICBT application. Therefore, plan of the day with optimization of the doses to target and OARs must be followed for each fraction.

Dosimetric comparison of manual forward planning with uniform dwell times versus volume-based inverse planning in interstitial brachytherapy of cervical malignancies.

AIM: Dosimetic comparison of manual forward planning(MFP) with inverse planning(IP) for interstitial brachytherapy(ISBT) in cervical carcinoma. BACKGROUND: Brachytherapy planning by MFP is more reliable but time-consuming method, whereas IP has been explored more often for its ease and rapidness. The superiority of either is yet to be established. METHODOLOGY: Two plans were created on data sets of 24 patients of cervical carcinoma who had undergone ISBT, one by MFP with uniform dwell times and another IP on BrachyVision 13.7 planning system with a dose prescription of 600 cGy. Isodose shaper was used for improving conformity & homogeneity. Dosimetric parameters for target and organs at risk (OARs) were recorded. Conformity index (COIN), dose homogeneity index (DHI), overdose index (OI), Coverage index (CI) and dose nonuniformity ratio (DNR) were calculated. RESULTS: Mean high risk clinical target volume: 73.05(±20.7)cc, D90: 5.51 Gy vs. 5.6 Gy (p = 0.017), V100: 81.77 % vs. 83.74 % (p = 0.002), V150: 21.7 % vs. 24.93 % (p = 0.002), V200: 6.3 % vs. 6.4 % (p=0.75) for IP and MFP, respectively. CI: 0.81(IP) and 0.83(MFP) (p = 0.003); however, COIN was 0.79 for both plans. D2cc of OARs was statistically better with IP (bladder 54.7 % vs. 56.1 %, p = 0.03; rectum 63 % vs. 64.7 %, (p = 0.0008). CONCLUSION: Both MFP and IP are equally acceptable dosimetrically. With higher dose achieved to the target, for a similar OAR dose, MFP provides greater user flexibility of dwell positions within the target as well as better optimization. Isodose shaper may be carefully used for fine tuning. Larger sample sizes and clinical correlation will better answer the superiority of one over the other.

Magnetic resonance image-based 3D volume interstitial brachytherapy using polyether ether ketone catheters in advanced cervical cancer - a feasibility study.

PURPOSE: A feasibility study of 3D volume-based interstitial brachytherapy using thermoplastic polyether ether ketone (PEEK) catheters in advanced cervical cancer MR-based brachytherapy, when MR-compatible applicators are not available. MATERIAL AND METHODS: Five cervical cancer patients received EBRT dose of 50 Gy in 25 fractions to whole pelvis using 3D conformal radiotherapy after standard pre-treatment evaluation. In our institute, interstitial brachytherapy (ISBT) is planned in BrachyVision TPS and routinely performed using stainless steel needles with Syed-Neblett template. Standard MR-compatible ISBT applicators were not available; therefore, the implant was carried out using PEEK catheters and Syed-Neblett template. The T1 and T2 MR and CT images of patients were acquired for treatment planning. Gross tumor volume (GTV), high-risk clinical target volume (HR-CTV), intermediate-risk clinical target volume (IR-CTV), and organs at risk (OARs) were delineated with the use of MR T2 weighted images, following GEC-ESTRO guidelines. Volumetric optimization was used for planning, and the treatment plan was executed with high-dose-rate (HDR) 192Ir Gammamed Plus device. RESULTS: The dose prescribed to HR-CTV was 30 Gy low-dose-rate (LDR) equivalent (5 Gy × 4 fractions). Doses to target volume and OARs were analyzed using dose volume histogram (DVH). Dose values were biologically normalized to equivalent doses of 2 Gy fractions (EQD2). The average tumor volume was 67 cc and the average D90 of HR-CTV was 29 Gy (5.7 Gy/fraction) EQD2. D100 of HR-CTV volume was 18 Gy (3.8 Gy/fraction) EQD2. The total doses of 2 cc of rectum and bladder were 70 Gy and 76 Gy EQD2 (3.71 Gy and 4.04 Gy dose/fraction), respectively. CONCLUSIONS: When the facilities for MR-compatible applicators are not available, MR-based ISBT is feasible with PEEK catheters using available resources for advanced cervical cancer. Doses to HR-CTV and IR-CTV were achieved, restricting doses to OARs as per GEC-ESTRO guidelines.

Fluorescence spectral diagnosis of malaria: a preliminary study.

BACKGROUND: Malaria is the most common disease transmitted by the bite by an infected female anopheles mosquito and caused by the plasmodium parasite. It is mostly prevalent in subtropical regions receiving abundant rain and supporting copious mosquito breeding. This disease is generally detected by the microscopic examination of blood films or antigen based rapid diagnostic test. Only occasionally the parasite DNA is detected using polymerase chain reaction in certain advanced, expensive laboratories. METHODS: An innovative spectral detection method based on the fluorescence spectra of a set of blood plasma biomolecules [tyrosine, tryptophan, nicotinamide adenine dinucleotide (NAD), and flavin adenine dinucleotide (FAD)] and red blood cell (RBC)-associated porphyrin is being evolved by our group. RESULTS: The research so far has exhibited sensitivity and specificity values exceeding 90% based on the spectral features of blood components of 14 malaria patients and 20 numbers of age adjusted normal controls. The fluorescent biomolecules go out of proportion when the malarial parasite breaks down the hemoglobin of blood. CONCLUSION: This technique has the potential to be used as an alternative diagnostic procedure for malaria since the instrumentation involved is portable and inexpensive. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_182.

Tackling a recurrent pinealoblastoma.

Pineoblastomas are rare, malignant, pineal region lesions that account for <0.1% of all intracranial tumors and can metastasize along the neuroaxis. Pineoblastomas are more common in children than in adults and adults account for <10% of patients. The management of pinealoblastoma is multimodality approach, surgery followed with radiation and chemotherapy. In view of aggressive nature few centres use high dose chemotherapy with autologus stem cell transplant in newly diagnosed cases but in recurrent setting the literature is very sparse. The present case represents the management of pinealoblastoma in the recurrent setting with reirradiation and adjuvant carmustine chemotherapy wherein the management guidelines are not definitive.

Cervical cancer detection by time-resolved spectra of blood components.

Fluorescence spectral techniques are very sensitive, and hence they are gaining importance in cancer detection. The biomarkers indicative of cancer could be identified and quantified by spectral or time domain fluorescence spectroscopy. The results of an investigation of time-resolved spectra of cellular components of blood obtained from cervical cancer patients and normal controls are given. The cancer indicative biomarker in this paper is porphyrin; it has a fluorescence decay time of 60% more in samples of cancer patients than those of normal controls. Based on such measurements, a randomized set comprising samples from cancer patients and controls (N=27 in total) could be classified with sensitivity (92%) and specificity (86%).

Treatment planning methods in high dose rate interstitial brachytherapy of carcinoma cervix: a dosimetric and radiobiological analysis.

Treatment planning is a trial and error process that determines optimal dwell times, dose distribution, and loading pattern for high dose rate brachytherapy. Planning systems offer a number of dose calculation methods to either normalize or optimize the radiation dose. Each method has its own characteristics for achieving therapeutic dose to mitigate cancer growth without harming contiguous normal tissues. Our aim is to propose the best suited method for planning interstitial brachytherapy. 40 cervical cancer patients were randomly selected and 5 planning methods were iterated. Graphical optimization was compared with implant geometry and dose point normalization/optimization techniques using dosimetrical and radiobiological plan quality indices retrospectively. Mean tumor control probability was similar in all the methods with no statistical significance. Mean normal tissue complication probability for bladder and rectum is 0.3252 and 0.3126 (P = 0.0001), respectively, in graphical optimized plans compared to other methods. There was no significant correlation found between Conformity Index and tumor control probability when the plans were ranked according to Pearson product moment method (r = -0.120). Graphical optimization can result in maximum sparing of normal tissues.

Quantification of uncertainties in conventional plan evaluation methods in Intensity Modulated Radiation Therapy.

PURPOSE: In Intensity Modulated Radiation Therapy (IMRT) dose distributions tend to be more complex and heterogeneous because of the modulated fluences in each beamlet of every single beam. These dose-volume (DV) parameters derived from the dose volume histogram (DVH) are physical quantities, thought to correlate with the biological response of the tissues. The aim of this study was to quantify the uncertainty of physical dose metrics to predict clinical outcomes of radiotherapy. METHODS: The radiobiological estimates such as tumor control probability (TCP) and Normal Tissue Complication Probability (NTCP) were made for a cohort of 40 cancer patients (10 brain;19 head & neck;11 cervix) using the DV parameters. Statistical analysis was performed to determine the correlation of physical plan quality indicators with radiobiological estimates. RESULTS: The correlation between conformity index (CI) and TCP was found to be good and the dosimetric parameters for optic nerves, optic chiasm, brain stem, normal brain and parotids correlated well with the NTCP estimates. A follow up study (median duration 18 months) was also performed. There was no grade 3 or 4 normal tissue complications observed. Local tumor control was found to be higher in brain (90%) and pelvic cases (95%), whereas a decline of 70% was noted with head & neck cancer cases. CONCLUSIONS: The equivalent uniform dose (EUD) concept of radiobiological model used in the software determines TCP and NTCP values which can predict outcomes precisely using DV data in the voxel level. The uncertainty of using physical dose metrics for plan evaluation is quantified with the statistical analysis. Radiobiological evaluation is helpful in ranking the rival treatment plans also.

Fluorescence spectral classification of iron deficiency anemia and thalassemia.

Thalassemia (Thal), sickle cell anemia, and iron deficiency anemia (IDA) are the most common blood disorders in many parts of the world, particularly in developing countries like India and Bangladesh. The well-established diagnostic procedure for them is the complete blood count (CBC); however, there is substantial confusion in discrimination between Thal and IDA blood samples based on such CBC. We propose a new spectral technique for reliable classification between the above two anemias. This is based on the identification and quantification of a certain set of fluorescent metabolites found in the blood samples of patients of Thal and IDA.

Accelerated partial breast irradiation using external beam radiotherapy-A feasibility study based on dosimetric analysis.

AIM: To investigate the feasibility of using External Beam radiotherapy for accelerated partial breast irradiation by a comparative tumour and normal tissue dose volume analysis with that of high dose rate interstitial brachytherapy. BACKGROUND: Accelerated Partial Breast Irradiation (APBI) is more clinically appealing because of the reduced treatment course duration and the irradiated area. Brachytherapy application is more dependent on the clinician's expertise when it is practised free hand without image guidance and a template. It happens to be an invasive procedure with the use of local anaesthesia which adds patient discomfort apart from its cost compared to External Beam Radiotherapy. But APBI with brachytherapy is more commonly practised procedure compared to EBRT owing to its previous reults. Hence in this research study, we intend to explore the use of EBRT with the radiobiological corrections for APBI in the place of brachytherapy. It is done as a dosimetric comparison of Brachytherapy treatment plans with that of EBRT plans. MATERIALS AND METHODS: The computed tomography images of 15 patients undergoing ISBT planning were simulated with conformal photon fields. Various dose volume parameters of each structure were obtained from the DVH generated in the brachytherapy and the simulated external beam planning which can correlate well with the late toxicity. The plan quality indices such as conformity index and homogeneity index for the target volume were computed from the dosimetric factors. The statistical p values for CI, HI and normal tissue dosimetric parameters were calculated and the confidence levels achievable were analysed. The dose prescribed in brachytherapy was 3400cGy in ten fractions. The equivalent prescription dose for the external beam radiotherapy planning was 3000cGy in five fractions applied with radiobiological correction. RESULTS: All the fifteen patients were with complete lung data and six were with left sided tumours having complete cardiac data. The lung dosimetry data and the cardiac dosimetry data of the patients were studied. Lower percentages of lung and cardiac V 20 and V 5 volumes were obtained with conformal planning. The conformity of radiation dose to the tumour volume was akin to the interstitial brachytherapy planning. Moreover the external beam planning resulted in more homogenous dose distribution. For the sampled population, the statistical analysis showed a confidence level of 95% for using EBRT as an alternate to multi catheter ISBT. CONCLUSION: The EBRT planning for Accelerated Partial Breast Irradiation was found to be technically feasible in the institution where the interstitial brachytherapy happens to be the only available technique as evident from the dose volume parameters and the statistical analysis.

Dosimetric comparison of high dose rate brachytherapy and intensity-modulated radiation therapy for cervical carcinoma.

Intracavitary brachytherapy is an integral part of radiotherapy for locally advanced gynecologic malignancies. A dosimetric intercomparison of high dose rate intracavitary brachytherapy (HDR_BT) and intensity-modulated radiotherapy in cervical carcinoma has been made in the present study. CT scan images of 10 patients treated with HDR_BT were used for this study. A sliding-window IMRT (IMRT_SW) and step-and-shoot IMRT plans were generated using 6-MV X-rays. The cumulative dose volume histograms of target, bladder, rectum and normal tissue were analyzed for both techniques and dose distributions were compared. It was seen that the pear-shaped dose distribution characteristic of intracavitary brachytherapy with sharp dose fall-off outside the target could be achieved with IMRT. The integral dose to planning target volume was significantly higher with HDR_BT in comparison with IMRT. Significant differences between the two techniques were seen for doses to 1 cc and 2 cc of rectum, while the differences in 1 cc and 2 cc doses to bladder were not significant. The integral doses to the nontarget critical and normal structures were smaller with HDR_BT and with IMRT. It is concluded that IMRT can be the choice of treatment in case of non-availability of HDR brachytherapy facilities or when noninvasive treatments are preferred.