Primary Central Nervous System Lymphoma: Focus on Indian Perspective

Early suspicion, withholding steroids, stereotactic biopsy, and high-dose methotrexate (HD-MTX) are essential for the treatment of primary CNS lymphoma (PCNSL) making its management in lower-middle-income countries (LMIC) challenging. Novel radiological methods, clinician awareness about the disease, and utilization of drugs like thiotepa and ibrutinib which can be given on an outpatient basis may allow better management of these patients in resource-poor settings. Combined with a late presenting demographic, this results in poorer outcomes in the Indian subcontinent as compared to its western counterparts. In this review, we summarize the currently available data on PCNSL in the Indian subcontinent. We also review the current standard of care for PCNSL and present potential modifications or research areas that may potentially improve outcomes in LMIC

Pierwotny śródczaszkowy bazaloidalny rak płaskonabłonkowy

Primary intracranial squamous cell carcinoma is extremely rare, with most cases arising from malignant transformation of dysembryogenetic lesions such as epidermoid and dermoid cysts. Intracranial squamous cell neoplasm arising de novo is even rarer and has been reported in only four patients to date. We herein describe a case of primary intracranial squamous cell carcinoma arising de novo in the right frontal lobe in a 35-year-old woman treated with a combination of surgery and postoperative conformal radiation. We have also shed light on the biology and the therapeutic options of this enigmatic tumour.Pierwotny śródczaszkowy rak płaskonabłonkowy jest wyjątkową rzadkością i w większości przypadków rozwija się w wyniku zezłośliwienia zmian o charakterze dysembriogenetycznym, np. torbieli naskórkowej lub skórzastej. Śródczaszkowy rak płaskonabłonkowy powstały de novo jest jeszcze rzadszy – dotąd opisano 4 takie przypadki. W niniejszej pracy przedstawiono przypadek nowotworu powstałego de novo w prawym płacie czołowym u 35-letniej chorej, którą z tego powodu poddano leczeniu chirurgicznemu i pooperacyjnej radioterapii konformalnej. Podano również informacje na temat biologii i możliwości leczenia tego zagadkowego guza

Impact of patient positioning on radiotherapy dose distribution: An assessment in parotid tumor

Purpose: We intended to study the impact of patient positioning on the dose distribution within target volume and organs at risk in patients with parotid malignancies treated with 3D conformal radiotherapy (3D-CRT) with photon wedge pair (WP) or intensity modulated radiotherapy (IMRT).Methods: Three patients with a non-Hodgkin’s lymphoma of the right parotid gland were consecutively immobilized using thermoplastic cast in 2 positions: supine with head in neutral position (HN) and with head turned 90° to the left side (HT). Images for treatment planning purpose were acquired in both positions. For both positions, photon WP plans and 5 field IMRT plans were generated, after contouring clinical target volume (CTV), planning target volume (PTV= CTV + 5 mm margin) and organs at risk (OAR). All plans were evaluated for target coverage and dose to OARs.Results: Both CTV and PTV were apparently larger in HN compared with HT (31.76±8.89 cc, 30.31±7.83 cc and 62.49±19.01 cc, 58.89±15.33 cc) respectively. The CI value for PTV was slightly better for HT compared to HN position in both the WP and IMRT plans. The homogeneity was comparable in both the head positions in case of WP plan. The mean HI of PTV was increased in case of IMRT plan at HT versus HN position (1.108 vs. 1.097). A change in head position from HN to HT with wedge pair plan resulted in a reduction of brainstem Dmax and Dmean. Lesser dose was observed in HN position for contralateral parotid. A difference of 0.9 Gy in the average Dmax to spinal cord was seen. The values of Dmean to mandible, oral cavity, ipsilateral and contralateral cochlea were higher in the HT position. A change in head position from HN to HT with IMRT plan resulted in a dose reduction in average Dmax to brainstem. The spinal cord Dmax increased at the HT position by 1.2 Gy. The dose to contralateral parotid and cochlea was comparable in both the positions. However, the Dmean to oral cavity was reduced at HT position. Whereas for IMRT versus wedge pair plan at head neutral position average Dmean to the contralateral parotid was reduced with the IMRT plan. A considerable reduction in Dmax to spinal cord and Dmean to ipsilateral cochlea was observed. A slight increase in average Dmax to brainstem and was observed with the IMRT plan. The doses to the remaining OARs were lesser in case of IMRT plan. For IMRT versus wedge pair plan at head tilt position slight increase in average Dmax to brainstem was observed in case of IMRT plan. A considerable reduction in Dmax to spinal cord and Dmean to ipsilateral cochlea was observed. The doses to the remaining OARs were reduced with IMRT plan.Conclusion: Change in head position from neutral to 90° contralateral tilt for wedge pair plan in parotid tumor may considerably reduce dose to the brainstem and spinal cord with a modest increase in dose to mandible, oral cavity, contralateral parotid, and bilateral cochlea. The alteration in head position has minimal impact on IMRT planning

Impact of head immobilization position on dose distribution in patients of brainstem glioma

Purpose: The purpose of this study is to investigate the impact of patient position (supine and prone) on conventional bilateral field, three dimensional conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) treatment plans in patients of brainstem glioma with a view to exploring the possibility of avoiding beam entry through immobilization accessories. Methods: Five patients of brainstem glioma were immobilized and scanned in supine and prone positions with a combination of head rest and thermoplastic cast. Each patient was planned with three techniques: (i) 2-fields bilateral (ii) 3-fields 3DCRT, and (iii) 5-fields IMRT. Plan quality was analyzed in terms of planning target volume (PTV) coverage and dose to various critical organs at risk (OAR) for both the supine and prone treatment positions. Results: In case of bilateral fields (parallel opposed) planning, the PTV coverage and dose to the OAR were almost similar for both the supine and prone positions. In 3DCRT plan, although the PTV coverage and dose to critical structures were comparable for both the supine and prone position, dose to cochlea was lower for the prone position plan. A modest decrease in maximum dose to optic nerves and mean dose to temporal lobes were also observed for the prone position plan. In IMRT plans, the PTV coverage and homogeneity were comparable in both the supine and prone positions. Reduction in average maximum and mean doses to all OARs with functional subunit (FSU) in series and parallel respectively was observed in the IMRT plan for prone position when compared to the supine position.Conclusion: Supine and prone positions resulted in almost similar dose distribution in all the three techniques applied. At some instances, the prone position showed better normal tissues sparing when compared to supine. Moreover, prone position is more likely to avoid attenuation due to immobilization devices and uncertainty in dose calculation under large inhomogeneities

Prognostic Stratification of GBMs Using Combinatorial Assessment of IDH1 Mutation, MGMT Promoter Methylation, and TERT Mutation Status: Experience from a Tertiary Care Center in India

AbstractThis study aims to establish the best and simplified panel of molecular markers for prognostic stratification of glioblastomas (GBMs). One hundred fourteen cases of GBMs were studied for IDH1, TP53, and TERT mutation by Sanger sequencing; EGFR and PDGFRA amplification by fluorescence in situ hybridization; NF1expression by quantitative real time polymerase chain reaction (qRT-PCR); and MGMT promoter methylation by methylation-specific PCR. IDH1 mutant cases had significantly longer progression-free survival (PFS) and overall survival (OS) as compared to IDH1 wild-type cases. Combinatorial assessment of MGMT and TERT emerged as independent prognostic markers, especially in the IDH1 wild-type GBMs. Thus, within the IDH1 wild-type group, cases with only MGMT methylation (group 1) had the best outcome (median PFS: 83.3 weeks; OS: not reached), whereas GBMs with only TERT mutation (group 3) had the worst outcome (PFS: 19.7 weeks; OS: 32.8 weeks). Cases with both or none of these alterations (group 2) had intermediate prognosis (PFS: 47.6 weeks; OS: 89.2 weeks). Majority of the IDH1 mutant GBMs belonged to group 1 (75%), whereas only 18.7% and 6.2% showed group 2 and 3 signatures, respectively. Interestingly, none of the other genetic alterations were significantly associated with survival in IDH1 mutant or wild-type GBMs.Based on above findings, we recommend assessment of three markers, viz., IDH1, MGMT, and TERT, for GBM prognostication in routine practice. We show for the first time that IDH1 wild-type GBMs which constitute majority of the GBMs can be effectively stratified into three distinct prognostic subgroups based on MGMT and TERT status, irrespective of other genetic alterations

Induction Therapy with Novel Agents and Autologous Stem Cell Transplant Overcomes the Adverse Impact of Renal Impairment in Multiple Myeloma

We investigated the impact of renal impairment (RI) on the outcome in multiple myeloma (MM) patients following induction and autologous stem cell transplantation (ASCT). Among 349 patients who received a first ASCT for MM, 86 (24.6%) had RI at diagnosis, defined as estimation of glomerular filtration rate (eGFR) <40 mL/min/1.73 m2 according to the modification of diet in renal disease (MDRD) formula. Post induction reversal of renal function occurred in 68 (79%) patients including complete renal response in 37.2%. Two hundred and fifty-one patients had received novel agents for induction; posttransplant complete response (CR) rates were 71.4% for patients with renal impairment (RI) versus 67.2% in those without RI, p = 0.23. The quality of stem cell collection and days to engraftment were similar except that patients with RI required higher transfusion numbers of packed red cells (p < 0.002) and platelets (p < 0.007). The median overall survival (OS) was 96 months (95% confidence interval [CI] 72.80–119.20) for patients with eGFR ≥40 mL/min, n = 195) versus 62 months (95% CI 28.7–95.3) for 56 patients with RI (eGFR <40 mL/min), p = 0.15. The 5-year OS was 64.6% versus 54.4%, respectively. The median progression-free survival (PFS) was 52 months (95% CI 36.3–67.7) for patients with eGFR ≥40 mL/min versus “not reached” for those with eGFR <40 mL/min p = 0.87; and the 5-year PFS was 48.1% versus 51%, respectively. We conclude that induction with novel agents results in reversal of renal dysfunction in the majority of patients. Consolidation with Hemopoietic Stem Cell Transplantation (HSCT) overcomes the adverse impact of RI on survival

Bleomycin induced flagellate erythema in a patient with thalamic mixed germ cell tumour: Report of a rare adverse effect

Bleomycin induced flagellate dermatitis is an uncommon and unique adverse effect. With the declining use of bleomycin, this complication is becoming increasingly infrequent in day-to-day clinical practice. We herein describe a case of a 13 year old male patient with left thalamic mixed germ cell tumour treated by multimodality approach, who developed flagellate erythema after two cycles of combination chemotherapy with bleomycin, etoposide and cisplatin (BEP). This brief report highlights the importance of awareness and timely identification and management of this dermatological toxicity in patients undergoing bleomycin based combination chemotherapy

Congenital peripheral primitive neuroectodermal tumor: A case treated successfully with multimodality treatment

Neonatal tumors comprise less than two percent of childhood malignancies. Most are solid tumors, most common histologies being teratoma and neuroblastoma. We encountered a child who was detected to have a right arm mass on antenatal sonogram, which was diagnosed to be a primitive neuroectodermal tumor involving the triceps on fine needle aspiration cytology performed in the post-natal period. The child was successfully treated with multimodality treatment consisting of surgery, chemotherapy and radiotherapy. We also discuss briefly the problems associated with therapy in neonatal period. A review of all cases reported to have congenital Ewing’s sarcoma family of tumors is presented. Novel therapies are needed to improve efficacy and decrease the devastating side effects of treatment in this age group

Radiation induced depigmentation disorder in two patients with breast cancer: Exploring a rare accompaniment

Radiation induced depigmentation disorder is a rare accompaniment. We herein report two patients of bilateral breast cancer developing depigmentation disorder, initially confined to the radiation portal with subsequent generalization within few months of completion of whole breast radiotherapy. Both these patients had no prior history of vitiligo or other autoimmune disorder. This brief report highlights the importance of awareness of this association in appropriate decision making in susceptible patients thereby preventing this morbidity and its psychological ramifications