Mono iso-centric VMAT planning for SBRT of multiple liver metastasis- A case report.

INTRODUCTION: Hepatocellular carcinoma (HCC) is the second most common cause of cancer mortality worldwide. The risk factors associated with the development of HCC are chronic Hepatitis B, Hepatitis C, and alcoholic cirrhosis. The standard care for HCC is surgical resection but the scope is limited for some patients. Continuous advancement of radiation therapy enabled the technique of stereotactic body radiotherapy (SBRT) as an option for the treatment of those cases for which surgery cannot be done. According to recent literature and meta-analysis, SBRT is an optimum treatment method with high local control with low toxicity. In SBRT, radiation is delivered with a smaller number of fractions than conventional radiation and employs high-precision delivery and accuracy with the help of image guidance. From a series of retrospective and prospective studies, it has been confirmed that SBRT achieves excellent local control in patients with early-stage inoperable, intermediate-stage, and advanced diseases. BACKGROUND: A 42-year-old male patient related to HBeAg infection and high AFP levels developed HCC BCLC Stage A was admitted to our department. There were two lesions with PTV volumes of 41.07 cc and 9.573 cc with a distance between them of 3.51 cm. These two lesions were treated with a mono-isocentric VMAT planning with SBRT technique. In this case, we present an unusual clinical practice of mono-isocentric treatment planning for treating multiple liver lesions. Since radiation therapy was viewed as the primary form of treatment because the patient wasn't an ideal candidate for surgery, SBRT was selected as the patient's primary modality of treatment because of the tiny volume of the two lesions and the normal liver volume (>700cc). Triple-phase 4DCT was performed for simulation to account for the motion of target volume and normal structures. After delineating the target volume and other normal structures, treatment planning was done with a dose of 45 Gray which was to be delivered in 5 fractions. Two PTVs were created with a margin of 3.0 mm to IGTV. Considering the positions of the lesions, a single isocentre plan was created using a 6MV FFF photon beam for both the PTVs with the VMAT technique. The treatment was carried through with 3 arcs, one coplanar, and the other 2 non-coplanar. At the time of treatment, after the proper positioning of the patient, one CBCT image was taken to match with the planned CT image acquired at the time of the simulation. After applying the translational and rotational errors, the patient was treated. RESULTS: The patient was treated successfully. After treatment, the condition of the patient was normal, and no toxicities have been observed in follow-up. CONCLUSION: Mono isocentric VMAT planning can be used for closely spaced lesions considering the position of lesions and other normal structures in the vicinity.

Chemotherapy-induced hand foot syndrome: comparative efficacy and safety of pharmacological prophylaxis - systematic review and Bayesian network meta-analysis.

BACKGROUND: Hand-foot syndrome (HFS) is one of the most common toxicities experienced by patients receiving systemic chemotherapy agents such as capecitabine and multikinase inhibitors such as sorafenib. Several randomised controlled trials (RCTs) have investigated the efficacy and safety of prophylactic agents such as pyridoxine, celecoxib, urea cream and cystine/theanine in managing HFS. This network meta-analysis (NMA) evaluated data from high-quality trials to provide strong evidence in forming recommendations to prevent systemic cancer therapy-induced HFS. OBJECTIVE: To examine the comparative efficacy and safety of interventions for preventing systemic chemotherapy-induced HFS in patients with cancer. METHODS: We searched PubMed, Embase and clinical trial registry for RCTs of interventions for preventing HFS. Bayesian NMA was performed to estimate the OR with 95% credible intervals (CrI) from both direct and indirect evidence. The outcome measures were the incidence of HFS (grade ≥1) and moderate to severe HFS (grade ≥2). Adverse drug reactions were discussed descriptively. RESULTS: A total of 15 RCTs with 2715 patients with 12 prophylactic strategies were included. The analysis showed only celecoxib could significantly prevent the incidence of moderate to severe HFS (grade ≥2) (OR 0.29, 95% CrI 0.13 to 0.68). But none of the preventive interventions could prevent the incidence of HFS (grade ≥1). CONCLUSION: Only celecoxib (200 mg two times per day) showed significant prevention of the incidence of moderate to severe HFS. Pyridoxine (400 mg once daily) and urea cream (10%) have to be evaluated further in larger randomised trials.

CMTM6 attenuates cisplatin-induced cell death in OSCC by regulating AKT/c-Myc-driven ribosome biogenesis.

CMTM6, a type 3 transmembrane protein, is known to stabilize the expression of programmed cell death ligand 1 (PD-L1) and hence facilitates the immune evasion of tumor cells. Recently, we demonstrated that CMTM6 is a major driver of cisplatin resistance in oral squamous cell carcinomas (OSCC). However, the detailed mechanism of how CMTM6 rewires cisplatin resistance in OSCC is yet to be explored. RNA sequencing analysis of cisplatin-resistant OSCC lines stably expressing Nt shRNA and CMTM6 shRNA revealed that CMTM6 might be a potential regulator of the ribosome biogenesis network. Knocking down CMTM6 significantly inhibited transcription of 47S precursor rRNA and hindered the nucleolar structure, indicating reduced ribosome biogenesis. When CMTM6 was ectopically over-expressed in CMTM6KD cells, almost all ribosomal machinery components were rescued. Mechanistically, CMTM6 induced the expression of C-Myc, which promotes RNA polymerase I mediated rDNA transcription. In addition to this, CMTM6 was also found to regulate the AKT-mTORC1-dependent ribosome biogenesis and protein synthesis in cisplatin-resistant lines. The nude mice and zebrafish xenograft experiments indicate that blocking ribosome synthesis either by genetic inhibitor (CMTM6KD) or pharmacological inhibitor (CX-5461) significantly restores cisplatin-mediated cell death in chemoresistant OSCC. Overall, our study suggests that CMTM6 is a major regulator of the ribosome biogenesis network and targeting the ribosome biogenesis network is a viable target to overcome chemoresistance in OSCC. The novel combination of CX-5461 and cisplatin deserves further clinical investigation in advanced OSCC.

Divided target optimization with volumetric modulated arc therapy planning to improve target coverage and homogeneity in lung radiation therapy.

PURPOSE: To investigate and evaluate the feasibility of a simple modified Divided Planning Target Volume (DPTV) optimization method in radiation therapy planning of lung cancer patients. METHODS: A cohort of 15 patients of Non-Small Cell Lung Cancer (13 patients stage III and two patients of stage II) who were previously treated with Concurrent Chemo Radiation Therapy were included in the study. The planning modality was Volumetric Modulated Arc Therapy, and the dose prescription was 60 Gray in 30 fractions. In this study, we attempted to replan by dividing the previous Single Planning Target Volume (SPTV) into a DPTV. All the treatment plans were revised and again optimized for DPTV with required dose constraints as in SPTV. The dosimetric parameters that were achieved for target and normal structures were recorded in both the optimization methods. RESULTS: Dosimetric target coverage (D95%) (p-value = 0.0001), dose homogeneity (p-value =0.0001) and conformity (p-value = 0.044) were improved by the DPTV optimization. The volume of the oesophagus receiving 35 Gy was found to be higher in the DPTV arm (p-value = 0.02) compared to the SPTV arm, but the volume of the oesophagus receiving 50 Gy was found to be similar (p-value = 0.122). CONCLUSION: In radiation therapy planning of lung cancer, the DPTV optimization method has better dose coverage to the target volume, homogeneity, as well as conformity than the stsndsrd SPTV method. Therefore, the DPTV optimization method can be a simple and efficient alternative to the SPTV method in lung cancer.

How prepared the radiotherapy centers are to deal with COVID-19 pandemic? A nationwide survey from 46 cancer centers across India.

Managing of radiotherapy department in many cancer centers in India has become very challenging during the COVID-19 pandemic. A radiotherapy center has to deal with multiple problems such as long treatment duration of each patient, high caseload on each radiotherapy machine, a limited number of qualified technical staff available, and equipment maintenance. For the department's smooth running, both the patient and healthcare worker must be safe from contacting COVID-19. A robust and planned strategy is required for prevention, screening, and awareness among all. To access our preparedness and evolve by gaining from other radiotherapy centers, a study was conducted using questionnaires and responses collected from different cancer centers in India.

An unusual response of recurrent breast cancer axillary lymphadenopathy to palliative radiotherapy: A case report.

INTRODUCTION: Radiotherapy has played a pivotal role in palliation of symptoms in progressive incurable stages of malignancies. Ionizing radiation has been employed to decrease cancer induced bone pain, control bleeding and mass effects from inoperable tumor with significant success. The advent of new systemic anti-neoplastic drugs has broadened options available for management of cancers in palliative intent. The outcome of systemic anti-neoplastic therapy in the role of palliation has received variable acceptance while radiotherapy has generally remained the workhorse for palliation. CASE REPORT: A young female with a diagnosis of left-sided breast cancer who had received adjuvant anthracycline based chemotherapy, but not whole breast radiotherapy, following lumpectomy had an axillary lymphnode recurrence three years later. Though the recurrence was salvaged with a radical mastectomy and followed up with a combination of taxane and platin-based chemotherapy, there was a recurrence of axillary lymph nodes during the course. Following six cycles of combination chemotherapy, the mass progressed to form a large ulcer with pain and discharge. The recurrent malignancy was diagnosed to be triple negative subtype upon microscopic and immunohistochemical study. OUTCOME: The ulcerated mass not only responded to palliative radiotherapy by complete healing of the ulcer, but it also led to improvement in overall performance score and quality of life as measured objectively. DISCUSSION: In triple negative subtype of breast cancer [TNBC], axillary lymphnodal recurrence is not uncommon after loco-regional surgery and peri­operative chemptherapy; particularly when adjuvant radiotherapy is omitted. Chemotherapy refractory axillary lymphnodal recurrence showing good response to palliative radiotherapy signifies the differing molecular signatures within TNBC subtype. CONCLUSION: Radiotherapy is an effective modality for loco-regional palliation of recurrent breast cancer, particularly TNBC subtype. It holds potency even when the disease is chemotherapy refractory and can improve subjective as well as objective quality of life parameters significantly.

RRBP1 rewires cisplatin resistance in oral squamous cell carcinoma by regulating Hippo pathway.

BACKGROUND: Chemoresistance is one of the major factors for treatment failure in OSCC. Identifying key resistance triggering molecules will be useful strategy for developing novel treatment methods. METHODS: To identify the causative factors of chemoresistance, we performed RNA sequencing and global proteomic profiling of human OSCC lines presenting with sensitive, early and late cisplatin-resistance patterns. RESULTS: From the common set of dysregulated genes from both the analysis, RRBP1 was identified to be upregulated in both early and late cisplatin-resistant cells with respect to the sensitive counterpart. Analysis of OSCC patient sample indicates that RRBP1 expression is upregulated in chemotherapy-non-responder tumours as compared to chemotherapy-responder tumours. Genetic (knockout) or pharmacological (Radezolid, represses expression of RRBP1) inhibition of RRBP1 restores cisplatin-mediated cell death in chemo-resistant OSCC. Mechanistically, RRBP1 regulates Yes-associated protein1 (YAP1), a key protein in the Hippo pathway to induce chemoresistance. The PDC xenograft data suggests that knockout of RRBP1 induces cisplatin-mediated cell death and facilitates a significant reduction of tumour burden. CONCLUSION: Overall, our data suggests that (I) RRBP1 is a major driver of cisplatin-resistance in OSCC, (II) RRBP1 regulates YAP1 expression to mediate cisplatin-resistance, (III) Radezolid represses RRBP1 expression and (IV) targeting RRBP1 reverses cisplatin-induced chemoresistance in advanced OSCC.

Tweaking of radiation and chemotherapy schedules is the new normal during the COVID-19 crisis: perspective from oncologists at a tertiary care health institute.

Patients with cancer are at a higher risk of infection with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-COV-2) than the general population. In India, it has become a significant health problem of utmost importance, and India's Government has issued health advisories. Lockdown brought many unforeseen problems for patients and hospitals, leading to confusion and chaos. The aim of this article is to identify various issues related to our hospital, follow-up, nutrition, treatment and psychosocial issues. Multiple changes were made in the hospital, departmental and treatment policy for cancer patients' convenience and safety. As India is in the peak of COVID-19, these types of modifications and modifications of treatment schedules will be the 'New Normal'.

Concomitant echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase rearrangement and epidermal growth factor receptor mutation in non-small cell lung cancer patients from eastern India.

BACKGROUND: In non-small cell lung cancer common driver mutations such as epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are usually mutually exclusive. This study aimed to elucidate the concurrence of EGFR mutation and ALK rearrangement in eastern India patients with primary lung adenocarcinoma and assess the response of EGFR tyrosine kinase inhibitor (TKI) therapy after 6 months in primary lung adenocarcinoma. METHODS: We retrospectively analyzed 198 adenocarcinomas for EGFR and ALK mutations. EGFR and ALK tests were done by real-time polymerase chain reaction and immunohistochemistry (IHC) techniques, respectively. Radiological response was assessed by Response Evaluation Criteria in Solid Tumors (version 1.1). RESULTS: EGFR/ALK co-alteration was found in 4 adenocarcinoma patients. All were males with advanced disease. Younger patients had exon 19 deletion whereas older ones showed exon 21 mutation. The initial option of ALK-TKI in all four patients was excluded straightaway due to the high-cost burden of ALK-TKI. Two of them showed a partial response while other two had stable disease after 6 months of EGFR TKI therapy. CONCLUSION: EGFR/ALK co-alterations in adenocarcinomas albeit rare do exist. The challenge of monetary hurdle in developing countries with ALK TKI therapy can be handled by giving only EGFR TKI in these cases of concomitant mutations. Future perspective in research could be finding an agent with the potential of dual inhibition of ALK and EGFR.

Efficacy and safety of nanosomal docetaxel lipid suspension based chemotherapy in gastric and gastroesophageal junction adenocarcinoma.

The current retrospective multicenter study evaluated the efficacy and safety of nanosomal docetaxel lipid suspension (NDLS; DoceAqualip) based chemotherapy in patients with gastric and gastroesophageal junction (GEJ) adenocarcinoma. The medical charts of patients with gastric and GEJ adenocarcinoma, who were treated with NDLS (50-75 mg/m2; 3 weekly cycles) based chemotherapy and followed-up from April 2014 to September 2018, were analyzed. The study endpoints included overall response rate (ORR) and disease control rate (DCR) in neoadjuvant and metastatic settings. Overall survival (OS) and safety were also evaluated. Of the 43 patients with gastric (n=39) and GEJ (n=4) adenocarcinoma, efficacy evaluation was available in 35 (neoadjuvant, 17/18 patients; metastatic, 18/25 patients). In the neoadjuvant setting, an ORR of 58.82% and a DCR of 94.11% were observed, whereas in the metastatic setting, the ORR was 77.77% and the DCR was 83.33%. In the neoadjuvant setting, at a follow-up ranging from 0.7 to 41.2 months, the median OS was not reached. In the metastatic setting, the median OS was 31.9 months at a follow-up ranging from 0.2 to 50.3 months. At least one adverse event (AE) was reported in 24 patients. Anemia, lymphopenia and thrombocytopenia were the most common hematological AEs, while nausea, vomiting and weakness were the most common non-hematological AEs. NDLS based treatment was well-tolerated without any new safety concerns. Overall, NDLS-based chemotherapy was effective and well-tolerated in the management of gastric and GEJ adenocarcinoma.

Synovial Sarcoma of Palmar Aspect of Hand and Survival: A Rare Case Report.

Synovial sarcomas of the hand are extremely rare entities than most soft tissue sarcomas. The location at finger is further rarer than carpus of the hand. Synovial sarcoma of the hand/finger initially confused with many diagnoses such as myositis, haematoma, synovitis, tendonitis, bursitis, and other inflammatory lesions and therefore needs careful handling of the case with proper evaluation. We report a case of synovial sarcoma of the palmar surface of the right hand at interface of thumb and index finger in a 22-year-old female. The case was initially misdiagnosed as an abscess/haematoma of the finger 10 years back and treated with wide local excision. Synovial sarcoma was diagnosed on microscopic examination of excised specimen. Patient developed recurrent lesion twice locally. During first recurrence, the patient was treated with wide excision followed by radiotherapy and chemotherapy. Second recurrence was with bony destruction at the same site and below elbow amputation was performed.

Choroidal Metastasis as Initial Presentation in Adenocarcinoma of Lung: A Case Report.

Vision impairment as an initial presentation detecting choroid metastasis in primary lung cancer is rare. Prevention or treatment of visual loss and improvement in quality of life can be achieved by treatment of intraocular metastasis. The survival of the patient in choroid metastasis with lung primary is poor with the median survival being 3.3 months. However, proper treatment may increase the quality of life and survival to an extent. We report a case of adenocarcinoma of lung in a female patient, presented initially with visual impairment as a result of choroidal metastasis and treated with external beam radiotherapy for choroidal metastasis followed by palliative chemotherapy. The patient was survived with improved vision and quality of life since last 12 months of diagnosis.

Digital Acrometastasis as Initial Presentation in Carcinoma of Lung A Case Report and Review of Literature.

Bony metastases develop in 30% of all the cancers, but out of which only 1% to 3% occurs in the hand. Lung is the most common site for acrometastasis, followed by breast and renal cell cancer. Metastases to the digits are with non-specific presentation. We reported a case of 79-year-old male patient with initial presentation of swelling over left index finger, which was found to be squamous cell carcinoma of finger on histopathological examination. He was subsequently diagnosed as a case of squamous cell carcinoma of lung with acrometastasis.

Squamous cell carcinoma of kidney and its prognosis: a case report and review of the literature.

Primary squamous cell carcinoma of the renal parenchyma is an extremely rare entity. The diagnosis of squamous cell carcinoma of the renal pelvis is usually unsuspected due to the rarity and inconclusive clinical and radiological features. Most of the patients are diagnosed at an advanced stage and are with poor outcome. Radical nephrectomy is the mainstay of the treatment. We reported a case of squamous cell carcinoma of the kidney in a 50-year-old female who presented with the right sided abdomen pain. The patient was treated with radical nephrectomy.

Dosimetric evaluation of 120-leaf multileaf collimator in a Varian linear accelerator with 6-MV and 18-MV photon beams.

In this study the dosimetric characteristics of 120-leaf multileaf collimators (MLCs) were evaluated for 6-MV and 18-MV photon beams. The dose rate, percentage depth dose, surface dose, dose in the build-up region, beam profile, flatness, symmetry, and penumbra width were measured using three field-defining methods: (i) 'Jaw only', (ii) 'MLC only', and (iii) 'MLC+Jaw'. Analysis of dose rate shows that the dose rate for 'MLC only' field was higher than that for 'Jaw only" and 'MLC+Jaw' fields in both the energies. The 'percentage of difference' of dose rates between 'MLC only' and 'MLC+Jaw' was (0.9% to 4.4%) and (1.14% to 7%) for 6 MV and 18 MV respectively. The surface dose and dose in the build-up region were more pronounced for 'MLC only' fields for both energies, and no significant difference was found in percentage depth dose beyond dmax for both energies. Beam profiles show that flatness and symmetry for both the energies were less than the 3%. The penumbra width for 'MLC only' field was more than that for the other two field-defining methods by (1 to 2 mm) and (0.8 to 1.3 mm) for 6-MV and 18-MV photon beams respectively. Analysis of 'width of 50% dose level' of the beam profiles at dmax to reflect the field size shows 1 to 2 mm more for 6-MV photons and 2.2 to 2.4 mm morefor 18-MV photons for 'MLC only' fields. The results of this study suggest that the characteristics of 120-leaf MLC system with 6 MV and 18 MV are same in all aspects except the surface dose, penumbra, dose in the build-up region, and width of 50% dose levels.

Comparison of dosimetric characteristics of 120-leaf and 80-leaf multi-leaf collimators in a Varian linear accelerator for a 6-MV photon beam.

In this study, the dosimetric characteristics of multileaf collimators (MLCs) with 120 leaves and 80 leaves were evaluated. The dose rate, percentage depth dose, surface dose, dose in the build-up region, beam profile, flatness, symmetry, and penumbra width were measured by three field-defining methods: (1) "Jaw only", (2) "MLC only", and (3) "MLC + Jaw", for a 6-MV photon beam with the two MLC systems. Analysis of the dose rate showed that the dose rate for the "MLC only" field was higher than that for the other two fields. The surface dose was more pronounced for the "MLC only" fields. The dose in the build-up region was higher for the "MLC only" fields, and no significant difference was found in the percentage depth dose (PDD) beyond the dose maximum point (d(max)) for both MLC systems. Beam profiles showed that the differences in flatness and symmetry for both systems were less than 3%. The penumbra width between 80 and 20% isodose levels for the "MLC only" field was more than that for the other two field defining methods. The widths of the 50% dose levels of the beam profiles were analyzed. The dosimetric characteristics of the two MLC systems were the same in all aspects except the surface dose, penumbra, the dose in the build-up region, and the width of the 50% dose levels.