Dose-Dense Docetaxel-Cyclophosphamide and Epirubicin-Cisplatin(ddDCEP): Analysis of an Alternative Platinum-Containing Regimen in 116 Patients with Early Triple Negative Breast Cancer.

We assessed the efficacy, tolerability, and cost-effectiveness of a novel neoadjuvant regimen comprising docetaxel-cyclophosphamide alternating with epirubicin-cisplatin (ddDCEP) administered biweekly for 16 weeks in 116 patients with early triple-negative breast cancer. This regimen achieved a high pathological complete response (ypT0/TisN0) rate of 55.2% and favorable survival outcomes (30-month event-free survival, 91.2%; overall survival, 97%). Febrile neutropenia was observed in 4.3% of patients, and 98% completed at least six of eight cycles. ddDCEP was more cost-effective than contemporary carboplatin-based regimens. This novel approach offers an economically viable and effective alternative to current chemoimmunotherapy regimens, and merits further investigation.

Feasibility study of total marrow lymphoid irradiation with volumetric modulated arc therapy: clinical implementation in a tertiary care center.

PURPOSE: Total marrow lymphoid irradiation (TMLI) with volumetric modulated arc therapy (VMAT) is challenging due to large treatment fields with multiple isocenters, field matching at junctions, and targets being surrounded by many organs at risk. This study aimed to describe our methodology for safe dose escalation and accurate dose delivery of TMLI treatment with the VMAT technique based on early experience at our center. MATERIALS AND METHODS: Computed tomography (CT) scans were acquired in head-first supine and feet-first supine orientations for each patient with an overlap at mid-thigh. VMAT plans were generated for 20 patients on the head-first CT images with either three or four isocenters in the Eclipse treatment planning system (Varian Medical Systems Inc., Palo Alto, CA) and the treatment was delivered in a Clinac 2100 C/D linear accelerator (Varian Medical Systems Inc., Palo Alto, CA). RESULTS: Five patients were treated with a prescription dose of 13.5 Gy in 9 fractions and 15 patients were treated with an escalated dose of 15 Gy in 10 fractions. The mean doses to 95% of the clinical target volume (CTV) and planning target volume (PTV) were 14.3 ± 0.3 Gy and 13.6 ± 0.7 Gy for the prescription doses of 15 Gy, and 13 ± 0.2 Gy and 12.3 ± 0.3 Gy for the prescription doses of 13.5 Gy, respectively. Mean dose to the lung in both schedules was 8.7 ± 0.6 Gy. The overall time taken to execute the treatment plans was approximately 2 h for the first fraction and 1.5 h for subsequent fractions. The average in-room time of 15.5 h per patient over 5 days leads to potential changes in the regular treatment schedules for other patients. CONCLUSION: This feasibility study highlights the methodology adopted for safe implementation of TMLI with the VMAT technique at our institution. Escalation of dose to the target with adequate coverage and sparing of critical structures was achieved with the adopted treatment technique. Clinical implementation of this methodology at our center could serve as a practical guide to start the VMAT-based TMLI program safely by others who are keen to start this service.

Outcome of radiotherapy for pituitary adenomas.

AIM: The aim of this study was to analyze the outcome and toxicities and its correlation to patient related and treatment related factors. BACKGROUND: Pituitary adenomas are treated by radiation therapy (RT) as one of the modalities along with surgery and medical therapy. RT to pituitary adenomas is a challenge due to adjacent dose limiting structures such as optic apparatus and hypothalamus. MATERIALS AND METHODS: Between January 2004 and December 2010, 94 patients treated for pituitary adenoma with RT who had hospital records of a minimum follow-up of 1 year were included in the analysis. Tests of correlation were done with regards to treatment factors. RESULTS: Male preponderance was noted in our patient population. Nonfunctioning and functioning tumors were equal in number in this series. Hypopituitarism was associated in 58.5% of patients prior to RT. Radiological tumor progression was seen in one patient (1/94) who had a nonfunctioning tumor. Among functioning tumors, biochemical remission was seen in 93.6% of patients at a median follow-up of 6 years. CONCLUSIONS: Visual complication was seen in 5.3% of patients and worsening or new onset hypopituitarism was seen in 6.4%. Conventional 3-field technique was associated with significantly more visual complication compared to Stereotactic Radiation Therapy (SRT) technique. Doses ≤50.4 Gy showed a trend of reduced rate of visual and endocrine complications with no compromise in efficacy.

Correlation Between Post-Radiosurgery Perinidal Hyperintensity and AVM Obliteration Following LINAC-Based Stereotactic Radiosurgery.

OBJECTIVE: We studied the correlation between new-onset perinidal hyperintensity (PH) on T2-weighted magnetic resonance imaging and obliteration of intracranial arteriovenous malformation (AVM) after stereotactic radiosurgery (SRS). METHODS: A retrospective study of 148 patients with an intracranial AVM who underwent SRS between September 2005 and June 2018 and had ≥1 radiological follow-up (early magnetic resonance imaging) 12-18 months after SRS was performed to analyze the correlation between PH (graded from 0 to 2) and AVM obliteration. RESULTS: Of the 148 patients, 95 were male. The mean patient age was 27.7 ± 12.4 years. Of the 148 AVMs, 105 (70.9%) were obliterated at a median follow-up of 27 months (interquartile range, 14-48 months). The cumulative 3-, 5-, 10-year obliteration rate was 51.8%, 70.8%, and 91.8%, respectively. New-onset PH was observed in 58 AVMs (39.2%; 50 obliterated and 8 not obliterated). No association was found between the pretreatment variables or dose delivered and the development of PH. Grade 2 PH was associated with the risk of symptoms developing compared with grade 1 PH (37.5% vs. 4%; P = 0.002). Symptomatic PH was more likely to develop in patients with a larger AVM (P = 0.05). On multivariate analysis, the presence of a single draining vein (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.3-6.8), a lower median AVM volume (OR, 0.97; 95% CI, 0.6-0.89), a mean marginal radiation dose (OR, 1.29; 95% CI, 1.02-1.64), and the presence of PH (OR, 3.16; 95% CI, 1.29-7.71) were independent predictors of AVM obliteration. CONCLUSIONS: The incidence of PH after SRS for AVM was 39.2%. PH was an independent predictor of AVM obliteration after SRS. Grade 2 PH and a larger AVM volume were associated with symptomatic PH.

Reverse Sneezing in Dogs: Observational Study in 30 Cases.

Reverse sneezing (RS) is a frequent reason for veterinary consultation, but there is scarce clinical information. The aim of this study was to describe clinical characteristics in a cohort of 30 dogs with RS. Signalment, clinical features, results of diagnostic tests, final diagnosis, and evolution were retrospectively evaluated. Sex and neuter status were equally distributed into diagnosis categories. A significantly higher representation of toys (<5 kg, 50%) and small-sized dogs (5−15 kg, 27%), in comparison to medium (15−30 kg, 17%) and large-sized dogs (>30 kg, 7%), was found. RS was the main owner concern in many of the cases (67%). Many cases presented chronic RS (60%, > 3 months), with more than one episode a week (60%). Most cases had an additional clinical respiratory sign (63%) and an unremarkable physical examination (63%). Inflammatory airway disorders were present in 57% of the cases, followed by anatomical−functional disorders (27%), and nasal/nasopharyngeal foreign bodies (10%). Two dogs (7%) remained as open diagnoses. Episodes of RS were persistent despite the treatment in 61% of the dogs with follow-up. Although some dogs manifest infrequent episodes of RS, being otherwise normal, RS should be considered a marker of potential irritation of the nasopharyngeal mucosa and should always be sufficiently investigated.

Aggressive malignant phyllodes tumor of breast with omental metastases - A case report.

Distant metastasis from malignant Phyllodes tumour (PT) is rare. They generally metastasize to the lung, bone, pleura, and liver. We present a very rare case of a 25-year-old woman with intraabdominal metastases from malignant phyllodes tumour of the breast. She presented with left breast lump and the biopsy was Phyllodes tumour. She underwent a two staged surgery; left modified radical mastectomy followed by left latissimus dorsi musculocutaneous flap cover. She received adjuvant radiation therapy to left chest wall. Following which she developed intrabdominal mass which was proven to be metastasis from Phyllodes tumour. She was then advised palliative chemotherapy. Malignant Phyllodes with distant metastases has a dismal prognosis. We propose it is preferable to have a CT Thorax and Abdomen as a staging workup for patients with malignant PT to identify those with poor prognosis.

Neoadjuvant chemotherapy with biosimilar trastuzumab in human epidermal growth factor receptor 2 overexpressed non-metastatic breast cancer: patterns of use and clinical outcomes in India.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is associated with poor prognosis and access to anti-HER2 treatment is still a challenge in lower-middle income countries. The availability of the biosimilar trastuzumab has improved access by lowering the costs. We report the pattern of use of neoadjuvant ± adjuvant trastuzumab and outcomes in patients with HER2-positive non-metastatic breast cancer treated with regimens incorporating shorter durations of therapy and the use of the biosimilar trastuzumab compared to the innovator. METHODS: We conducted a retrospective analysis of patients with non-metastatic HER2-positive breast cancer treated with neoadjuvant ± adjuvant trastuzumab (innovator (n = 34 (33%)) and biosimilar (n = 70 (67%)) manufactured by Biocon Biologics) with chemotherapy. Information regarding chemotherapy regimens, duration of trastuzumab use (≤12 weeks and >12 weeks), pathological response (Miller Payne grade), disease free survival (DFS), overall survival (OS) and safety data were collected from electronic medical records. RESULTS: A total of 135 patients were analysed with a median age of 51 years (range: 23-82); of these, 57% were postmenopausal, 31.8% were hormone receptor positive and 62.9% had stage III disease. The overall pathological complete response (p-CR) in both breast and axilla increased to 37.6% in patients treated with trastuzumab preoperatively as compared to 22.2% in patients who did not receive any trastuzumab. Patients receiving innovator trastuzumab and biosimilar trastuzumab showed a p-CR of 28.5% and 41.7%, respectively. At a median follow-up of 42 months (range: 3-114), there were 18 relapses and 11 deaths. The 3-year DFS was 87.1% and OS was 92.2%. Cardiac dysfunction developed in 4 of 78 (5.1%) evaluable patients. CONCLUSION: Access to anti-HER2 therapy in the treatment of non-metastatic HER2-positive breast cancer in resource-constrained settings has improved significantly with the availability of the biosimilar trastuzumab. Imbalances in patient profiles at baseline in routine clinical practice led to inconclusive outcomes of ≤12 weeks versus >12 weeks trastuzumab treatment. However, on the basis of historical data, patients could be offered shorter duration of trastuzumab when a standard 1-year treatment of adjuvant trastuzumab is not feasible in resource-constrained settings. The p-CR using the biosimilar trastuzumab in neoadjuvant treatment has been observed to be comparable to the innovator trastuzumab.

Functional assessment of time course microarray data.

MOTIVATION: Time-course microarray experiments study the progress of gene expression along time across one or several experimental conditions. Most developed analysis methods focus on the clustering or the differential expression analysis of genes and do not integrate functional information. The assessment of the functional aspects of time-course transcriptomics data requires the use of approaches that exploit the activation dynamics of the functional categories to where genes are annotated. METHODS: We present three novel methodologies for the functional assessment of time-course microarray data. i) maSigFun derives from the maSigPro method, a regression-based strategy to model time-dependent expression patterns and identify genes with differences across series. maSigFun fits a regression model for groups of genes labeled by a functional class and selects those categories which have a significant model. ii) PCA-maSigFun fits a PCA model of each functional class-defined expression matrix to extract orthogonal patterns of expression change, which are then assessed for their fit to a time-dependent regression model. iii) ASCA-functional uses the ASCA model to rank genes according to their correlation to principal time expression patterns and assess functional enrichment on a GSA fashion. We used simulated and experimental datasets to study these novel approaches. Results were compared to alternative methodologies. RESULTS: Synthetic and experimental data showed that the different methods are able to capture different aspects of the relationship between genes, functions and co-expression that are biologically meaningful. The methods should not be considered as competitive but they provide different insights into the molecular and functional dynamic events taking place within the biological system under study.

A Rare Case of Gastric Metastasis in Ewing's Sarcoma of the Femur.

The stomach is a very unusual site of metastasis. Published reports on metastatic lesion in the stomach is generally limited to single case reports and case series. Gastric metastasis in an Ewing's sarcoma is extremely rare and has been reported in English literature but once to our knowledge. We present a case report of Ewing's sarcoma of the right proximal femur metastasizing to the stomach. A young female treated for Ewing's sarcoma of the femur in 2012 presented with gastric metastasis after four years of disease-free interval. She was treated with irinotecan-based chemotherapy followed by total gastrectomy with esophagojejunal anastomosis and radiation therapy. At one-year follow-up, she was disease free.

Is the Deep Inspiration Breath-Hold Technique Superior to the Free Breathing Technique in Cardiac and Lung Sparing while Treating both Left-Sided Post-Mastectomy Chest Wall and Supraclavicular Regions?

AIMS: To evaluate the efficacy of the deep inspirational breath-hold (DIBH) technique and its dosimetric advantages over the free breathing (FB) technique in cardiac (heart and left anterior descending artery [LAD]) and ipsilateral lung sparing in left-sided post-mastectomy field-in-field conformal radiotherapy. DIBH is highly reproducible, and this study aims to find out its dosimetric benefits over FB. MATERIALS AND METHODS: Nineteen left-sided mastectomy patients were immobilized using breast boards with both arms positioned above the head. All patients had 2 sets of planning CT images (one in FB and another in DIBH) with a Biograph TruePoint HD CT scanner in the same setup. DIBH was performed by tracking the respiratory cycles using a Varian Real-Time Position Management system. The target (chest wall and supraclavicular region), organs at risk (OARs; ipsilateral lung, contralateral lung, heart, LAD, and contralateral breast), and other organs of interests were delineated as per the RTOG (Radiation Therapy Oncology Group) contouring guidelines. The single-isocenter conformal fields in the field treatment plans were generated with the Eclipse Treatment Planning System (Varian Medical Systems) for both FB and DIBH images, and the doses to the target and OARs were compared. The standard fractionation regimen of 50 Gy in 25 fractions over a period of 5 weeks was used for all patients in this study. RESULTS AND DISCUSSION: The target coverage parameters (V95, V105, V107, and D_mean) were found to be 97.8 ± 0.9, 6.1 ± 3.4, 0.2 ± 0.3, and 101.9 ± 0.5% in the FB plans and 98.1 ± 0.8, 6.1 ± 3.2, 0.2 ± 0.3, and 101.9 ± 0.4% in the DIBH plans, respectively. The plan quality indices (conformity index and homogeneity index) also showed 1.3 ± 0.2 and 0.1 for the FB plans and 1.2 ± 0.3 and 0.1 for the DIBH plans, respectively. There was a significant reduction in dose to the heart in the DIBH plans compared to the FB plans, with p values of nearly 0 for the V5, V10, V25, V30, and D_mean dosimetric parameters. The difference in ipsilateral lung doses between FB and DIBH showed statistically significant p values, and the differences in mean doses were found to be 7, 15.7, 11.8, and 10.7% for V5, V20, V30, and D_mean, respectively. There was a significant reduction in dose to the LAD in the DIBH compared to the FB plans. CONCLUSIONS: DIBH resulted in significant reductions in doses to the heart, LAD, and lungs, since with this technique there was an increase in the distance between the target and the OARs. With appropriate patient selection and adequate training, the DIBH technique is acceptable and achievable for radiotherapy to the chest, and therefore should be considered for all suitable patients, as this could result in fewer radiotherapy-related complications. However, this technique is time-consuming, since the setup is complex, results in an increased time for treatment delivery, and needs patient cooperation and technical expertise.

An unusually long survival of a patient with glioblastoma of spinal cord: a case report.

Primary glioblastoma of spinal cord are rare and are associated with poor survival especially in adults. We report a case of glioblastoma of thoracic spinal cord (D3 to D6) in an adult treated with partial resection surgery and radiation therapy with a survival of six years with good quality of life. The patient had paraplegia at presentation but improved after surgery and radiation therapy to grade 4 in both lower limbs. After 5 years, he developed new lesion in a different location of the spine (L1, L2 & L5) along with multiple lesions over entire spine and was treated with radiation therapy and a year later developed a new lesion intracranially in the posterior fossa involving cerebellopontine angle region infiltrating brainstem. He was treated with palliative radiotherapy and is on chemotherapy with Temozolomide and is still alive with ability to do activities of daily living at the time of this report. Radiation therapy provided prolonged local control with effective palliation of symptoms and good quality of life in this patient enabling to do activities of daily living.