Ядерная медицина и лучевая терапия

Introduction: Radiotherapy is utilised in the treatment of many cancers, but its efficacy is limited by normal tissue toxicity and new radiotherapy techniques are thus urgently sought. The AP endonuclease APE1 is involved in repair of single strand DNA damage through the break excision repair (BER) pathway and altered levels of APE1 have been found in some cancers. In this study, we investigated the effects of APE1 inhibition, using the APE1-specific inhibitor CRT0044876 (CRT), in tumour cells following exposure to either high dose-rate (HDR) or low dose-rate (LDR) X-irradiation.

Materials and Methods: Treatment efficacy was assessed by clonogenic assay followed by isobologram analysis to assess potential synergy. Cell cycle distribution was assessed by propidium iodide staining followed by flow cytometry. Induction of DNA damage and repair was assessed by single cell gel electrophoresis and by H2A.X phosphorylation.

Results: In isobologram analysis of clonogenic assays, combinations of CRT and both HDR and LDR X-irradiation resulted in supra-additive levels of cytotoxicity. Cell cycle analysis showed that, while CRT had no effect on cell cycle distribution, HDR or LDR X-irradiation, and CRT-HDR or CRT-LDR combination treatment induced significant G₂/M arrest. However, CRT-HDR combinations induced significantly less G₂/M accumulation than HDR alone. Analysis of DNA damage indicated that treatment with HDR or LDR X-irradiation and CRT-HDR and CRT-LDR combinations induced significant double-strand DNA damage. Cells treated with CRT-HDR exhibited a significant reduction in γH2A.X foci 24 h after treatment compared to 1 h, suggesting induction of DNA repair mechanisms. However, in cells treated with CRT-LDR, there was no significant difference between H2A.X phosphorylation at 24 h compared to 1 h, suggesting disruption of dsDNA repair pathways.

Conclusions: Pharmacological inhibition of APE1 enhances the cytotoxicity of high dose-rate and low dose-rate X-irradiation by different mechanisms.

In routine oncological 18F-fluorodeoxyglucose positron emission tomography (FDG-PET/CT) scan, the patients rest in a quite, dimly lit room for 60 minutes after intravenous (IV) injection of FDG and they are instructed not to move during this time (uptake phase) before FDG-PET/CT scanning to prevent and decrease unwanted FDG accumulations on muscle traces caused by muscle movements. In conditions of patient inconsistency, undesirable activities can be seen and reach high levels making difficult or even impossible to interpret the images. Different muscle groups form various physiological or over- physiological uptake patterns depending on their specific motion. Herein we represent a good didactic example to this phenomenon.

We report the incidental identification of an unsuspected Pigmented Villonodular Synovitis (PVNS) in a patient of known thyroid malignancy (poorly differentiated thyroid carcinoma, PDTC) who underwent whole body 18 Fluorine Flurodeoxyglucose Positron Emission Tomography Computed Tomography (18F FDG PET CT). FDG PET CT showed a FDG avid enhancing lesion in the subscapularis muscle near coracoid process of left scapula. A subsequent MRI showed a lesion anterior to the left glenoid in close proximity to the subcapsularis tendon suggestive of PNVS arising from the subcapsular bursa. This case highlights the non oncological utility of FDG PETCT in musculoskeletal disorders like PVNS.

Sternal infections are a major cause of morbidity and mortality in patients undergoing cardiac surgery. They occur in 1% to 3% of patients who undergo open-heart surgery and carry a moderately high mortality rate. Sternal infections can range from minor, superficial infections to open mediastinitis with invasion of the sternum, heart, and great vessels. Infection can lead to partial or complete separation of bony sternum thus compounding the problem. Identifying osteomyelitis (OM) is a challenge to the surgeons especially in the postoperative setting. Although clinically presence of fever and leukocytosis along with sternal wound dehiscence suggests deep infection. Localization and ascertaining the extent of sternal infection is difficult. Treatment entails surgical debridement with closed irrigation, open-wound packing, or muscle or omental flap procedures, as well as antibiotic therapy. In sternal OM, delineation of sinus tracts into the various planes of anterior mediastinal tissues is essential to achieve proper surgical drainage and antibiotic cover. This is exclusively achieved by Gallium infection imaging and additional use of SPECTCT (Single photon emission computed tomography). Only when the postoperative site is devoid of residual infection, thoracic and trunk reconstruction can be performed to provide stability to sternal dehiscence.

Purpose: To assess brain tumor displacements between skull based and soft-tissue based matching during CTMRI fusion for a total of 35 brain lesions.

Methods: Twenty-five patients who underwent CT and MRI scans in the same day were retrospectively recruited into the study. Semi-automatic skull based fusion was first performed and reviewed on a Treatment Planning System (TPS). A secondary fine-tuning of the fusion was then performed, if mismatch was observed in the tumor or neighboring soft-tissue, using nearby visible soft-tissue, such as gyri, sulci, and fissures. Two physicists fine-tuned the secondary fusion until the best match could be agreed upon. The resulting rotations and translations between the two fusions were recorded, which indicated local displacements between skull based and soft-tissue based matching. We further created a PTV by expanding a 2 mm margin around the GTV after skull-based fusion, and then evaluated the coverage of the GTV within the PTV after fine tuning with soft-tissue based fusion.

Results: In 29 of the 35 lesions, minor to no mismatch was found between the soft-tissue and skull based fusions. The corresponding translational and rotational shifts were 0.05 ± 0.63 mm (LR), 0.01 ± 0.79 mm (AP), 0.37 ± 1.01 mm (SI); -0.15 ± 0.67° (pitch), -0.19 ± 0.34° (yaw), and -0.12 ± 0.49° (roll). Thus the GTV, after soft-tissue based fusion, was 100% covered by the PTV. However, in the remaining 6 lesions in the study, noticeable displacements were observed between the skull and soft-tissue based fusions. Excluding an outlier lesion, the mean translational and rotational shifts for 5 of the 6 remaining lesions were 0.90 ± 2.15 mm (LR), 1.50 ± 2.27 mm (AP), -1.01 ± 1.83 mm (SI); -1.42 ± 3.12°(pitch), 0.02 ± 0.83°(yaw), and -0.17 ± 0.68°(roll). For the outlier lesion, the GTV was nearly missed by the PTV, and for the rest of the 5 lesions, the mean coverage of the GTV was 98.9% within the PTV.

Conclusion: In a small portion of lesions, our study showed noticeable brain tumor displacement with typical patient setup in CT and MRI scans when using skull based fusion in comparison with soft-tissue fusion. Careful review of the skull based fusion is recommended by examining the match with nearby soft-tissue and/or tumors. If fusion deviations are found, it is also recommended to consider adding a margin to the GTV to account for such variations, since such variations could potentially affect target localization accuracy at the time of treatment.

Purpose: The aim of this study was, using deformable image registration (DIR), to evaluate alteration of dose distribution caused by patient’s anatomical structure changes during a two-phase intensity-modulated radiotherapy (IMRT).

Methods: IMRT consisted of an initial plan delivering 53 Gy to gross tumor volume (GTV) and 45 Gy to elective volumes and a boost plan delivering 16.96 Gy to GTV. The subjects were 10 patients with head and neck cancer who underwent computed tomography (CT) scans twice (first CT before treatment and second CT before boost). A sum of the initial and the boost plans for the first CT was Original total plan. Using DIR, the original boost and a modified new boost plan were recalculated on the second CT and summed with the initial plan to create total plans: DIR plan and modified DIR plan.

Results: Mean dose (Dmean) of the ipsilateral and contralateral parotids were increased by 8.0% (P<0.01) and 6.8% (P<0.05) in DIR plan compared with Original total plan. Compared with DIR plan, modified DIR plan reduced Dmean of the ipsilateral parotid (P<0.01). Dose to 95% of the volume (D95) to clinical target volume for GTV (CTV1) of DIR plan was significantly higher than that of Original total plan (P<0.01) and modified DIR plan (P<0.01).

Conclusions: Dose summation using DIR demonstrated that the body shrinking during IMRT significantly increased the doses of both parotids and CTV1. Modified DIR plan compensated the increases in doses of the ipsilateral parotid and CTV1.

Non-small cell lung cancer ranks among the most lethal cancers worldwide. The rate of epidermal growth factor receptor (EGFR) mutations and echinoderm microtubuleassociated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) gene fusion is the most common in younger age, non-smoking Asian adenocarcinoma lung cancer patients. EGFR mutations and ALK gene rearrangements are known to be mutually exclusive and as mutual causes of resistance to EGFR-tyrosine kinase inhibitors (TKIs) or ALK-TKIs. However, rarely such co-alterations do co-exist in some clinical cases. Here we report a 62 year old male, heavy smoker with cough, hemoptysis and fatigue. Histopathological examination of bronchoscopic guided biopsy showed adenocarcinoma histology. Staging evaluation, he was found to have stage IV disease on positron emission tomography-computed tomography scan. The biopsy blocks tested positive for both EGFR mutation and ALK fusion. Patient was initiated on tablet Gefitinib 250 mg once daily. To the best of our knowledge, there has been no report of dual EGFR mutation and ALK fusion positivity from India.

Lung cancer is the leading cause of cancer deaths worldwide. Recently, there is an emerging interest on lung cancer screening which can increase the incidence of lung cancer among the population in the coming. There was 20% reduction in mortality from lung cancer in the National Lung Screening Trial (NLST) with the use of low-dose computed tomography. NLST criteria included people between ages 55-74 years, ≥30 pack-years of smoking or <15 years since cession of smoking. Patients with early stage disease and young age, good performance status and pulmonary function tests are treated with curative intent including either surgery or combined treatment modalities, concurrent chemo-radiation therapy. Treatment of choice for medically inoperable group of patients is definitive radiation therapy (RT). Patients with poor pulmonary function (PF) are considered a contraindication to definitive RT. We discuss the role of RT and importance of dose escalation to achieve improved local control rates among patients with different stages of non-small cell lung carcinoma (NSCLC) with poor PF. Till date, there are no clinical practice guidelines or randomized prospective phase III studies to treat this subset of high-risk patients with RT dose escalation using advanced RT techniques like intensity modulation radiation therapy, volumetric modulated arc therapy (IMRT, VMAT). Also, there is limited evidence on the use of newer chemotherapy regimens with advanced RT techniques for NSCLC patients with poor PF except for retrospective data or phase I/II studies. Different tools to estimate and measure radiation pneumonitis (RP) along with the review of the published data on RP was done. Impact of newer RT techniques along with adaptive RT using mid-course PET scans for RT planning using photons and protons are also addressed.

Aim: to evaluate tumor control, toxicity and cosmesis in patients with relapse of basal cell carcinoma (BSC) who underwent high-dose-rate brachytherapy (HDR-BT)using a regimen of hypofractionation.

Case presentation: A 93-year-old male, Karnosky Performace Status 90%, was diagnosed to have a relapse of BSC. A biopsy confirmed a relapse of BSC. The patient underwent HDR-BT with 192 Ir. The prescription dose of 50 Gy in 20 fractions of 2.5 Gy was delivered daily. The Common Terminology Criteria for Adverse Events (CTCA v4.0) toxicity scale was used to asses acute toxicity and the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) scale was used to asses late toxicity related to cosmesis. The treatment was well tolerated. Clinically, the lesion completely regressed. The skin acute toxicity was grade 2 CTCA v4.0 and late toxicity grade 1EORTC. When the patient was consulted about his cosmetic result, he was satisfied. At the median follow-up of 7 months, the patient was alive and disease-free.

Conclusion: the HDR-BT can be an effective and safe treatment option for selected elderly patients with relapse skin cancer.

The optically stimulated luminescence (OSL-BeO) dosemeter is increasingly being used as a dosimetric technique in various fields such as medical dosimetry. According to our fixed dose protocol, the activities of 3.7-7.4 GBq I-131 source is used for thyroid carcinoma therapy. The in house calibration process for usage of OSL’s at hospital was arranged according to the encapsulated I-131. The measurement point was planned in three different radial distances from source free in air. The dose-rate measurement was done by Geiger-Muller (GM), and then three pieces of OSL was placed in the same positions for one hour. The inverse square law consistency was found (R2=0.99). The calibration coefficient was calculated. For determining the performance of OSL at different dose rates, it used for personnel and patient dosimetry. The average annual dose/2mon to the whole body for all staff by OSL were 0.80 mSv. After administration of 3.7 GBq (100 mCi) therapeutic dose to selected patients, the average pectoral dose was 97.5+32.6 mSv. This calibration process is helpful for confidence of OSL detectors used for dosimetry of staff and patients treated with high activity I-131.

Aims: High dose 131I-meta iodobenzylguanidine (131I-mIBG) combined with radiosensitizing topotecan and peripheral blood stem cell support is a promising treatment regimen for children with neuroblastoma (NB). Here we present our first experiences, with particular focus on in vivo whole-body dosimetry and radiation exposure to family caregivers and hospital staff.

Methods: Five children with relapsed or refractory NB were treated during 2012-2014. 131I-mIBG was administered in two fractions at two weeks apart, aiming for a total whole-body radiation-absorbed dose of 4 Gy. The 131I-mIBG activity for the 2nd administration was calculated on the basis of the measured whole-body dose following the 1st administration. Patients were isolated in a lead-shielded room, and all caregivers and staff received radiation safety training, and carried an electronic personal dosimeter.

Results: The total administered activity ranged from 5.1 to 28.6 GBq (median: 22.9 GBq), resulting in effective whole-body doses ranging from 2.1 to 4.3 Gy (median: 3.8 Gy). Two out of five patients deviated from the anticipated dose exposure defined by the treatment protocol; one patient received 4.3 Gy after a single administration, and for one patient the total whole-body dose was lower than anticipated (2.1 Gy). Radiation dose to family caregivers ranged from 0.1 to 8.0 mSv. For staff members, the overall radiation dose was low, and provided no concern regarding personal dosimetry.

Conclusion: High-dose 131I-mIBG treatment of children with NB has been successfully established at our institution. Radiation doses to caregivers and hospital staff are acceptable and in compliance with national and international guidelines. Two out of five patients deviated from the anticipated dose exposure, hence, accurate dosimetry-guidance during administration of high dose 131I-mIBG treatment is necessary.

Chronic Myeloid Leukemia (CML) is a stem cell disorder, characterized by the translocation of 9th chromosome of Abelson (ABL) gene to the 22th chromosome of breakpoint cluster region (BCR) gene. Consequently, translocation results into the chimeric oncogene BCR-ABL which encodes the BCR-ABL oncoprotein. CML is mainly a disease of adults but it can occur in any stage of life and it accounts around 15% of the all the types of leukemia. Various methods have been used to combat this disease like Chemotherapy, Radiation therapy; tyrosine kinase inhibitors etc., Imatinib as a tyrosine kinase inhibitor has dramatically improved the survival rate of CML patients, hence can be referred as first generation drug against the CML. Later on, recurrence of the disease in some treated patients has also been seen probably due to mutation in oncogenes. Researchers have started to find out more efficient tyrosine kinase inhibitors which can work on mutated oncoprotein and which can be referred as second or third generation drugs. In this review, special emphasis have been given to the carcinogenic mechanism of abnormal fusion of the BCR-ABL genes, current therapeutic options to prevent this disease, and Systems Biology approach to explore the CML associated biochemical pathways. Various advantages and disadvantages of the all therapeutic options to combat CML have also been discussed.

We report a case of a young Indian male who had an incidental abnormal focal uptake of 99mTechnetium-MIBI (Methoxy Isobutyl Isonitrile) in the right lobe of thyroid while undergoing 99mTc-MIBI myocardial perfusion gated SPECT (Single Photon Emission Computed Tomography) imaging as a part of his myocardial ischemia status evaluation. This focal uptake was eventually detected to be a malignant thyroid nodule for which he underwent total thyroidectomy. His biopsy was reported as Hurthe cell nodule. Though incidental detection of thyroid, breast and lung malignant pathology on 99mTc- MIBI myocardial perfusion scans is well known, this case is a reminder and exemplifies the potential of 99mTc-MIBI not only as an excellent myocardial perfusion agent but also as a non specific tumour tracer (for its larger usage as a tracer for neoplastic survey).

Patients with meningioma usually undergo surgery with curative intent, based on conventional imaging techniques such as computer tomography and magnetic resonance imaging. However, unidentified tumor lesions at the time of surgery can render the surgery non-curative. In the last decade, positron emission tomography (PET) with somatostatin receptor ligand DOTA-D-Phy1 -Tyr3 -octreotide labeled with gallium-68 (68Ga-DOTATOC) has increasingly become an important tool in the management of meningiomas compared to conventional imaging. However, its indications are not well defined. We present a case of a 60-year old woman who presented with a recurrence of an anaplastic meningioma in the right occipital region, 29 months after the primary excision of an initial diagnosed atypical meningioma. Despite two subsequent surgical excisions and two courses of stereotactic radiation treatment over a period of 42 months, the tumor continued to recur at different sites. A PET scan performed with the tracer 68Ga-DOTATOC later revealed additionally small positive lesions, suggesting a meningioma composed of multiple foci. As meningioma recurrences, particularly with multiple foci, have a significant impact on determining treatment for the individual patient, a routine 68Ga-DOTATOC PET could help avoid non-curative surgery by identifying patients with multifocal disease.