Multi-Institutional Clinical Outcomes of Biopsy Gleason Grade Group 5 Prostate Cancers Treated With Contemporary High-Dose Radiation and Long-Term Androgen Deprivation Therapy.

AIMS: This multicentric retrospective study reports long-term clinical outcomes of non-metastatic grade group 5 prostate cancers treated with external beam radiotherapy (EBRT) alone with long-term androgen deprivation therapy (ADT). MATERIALS AND METHODS: Patients treated across 19 institutions were studied. The key endpoints that were evaluated were 5-year biochemical recurrence-free survival (bRFS), metastases-free survival (MFS), overall survival, together with EBRT-related acute and late toxicities. The impact of various prognostic factors on the studied endpoints was analysed using univariate and multivariate analyses. RESULTS: Among the 462 patients, 88% (405) had Gleason 9 disease and 31% (142) had primary Gleason pattern 5. A prostate-specific membrane antigen positron emission tomography-computed tomography scan was used for staging in 33% (153), 80% (371) were staged as T3/T4 and 30% (142) with pelvic nodal disease. The median ADT duration was 24 months; 66% received hypofractionated EBRT and 71.4% (330) received pelvic nodal irradiation. With a median follow-up of 56 months, the 5-year bRFS, MFS and overall survival were 73.1%, 77.4% and 90.5%, respectively. Primary Gleason pattern 5 was associated with worse bRFS, MFS and overall survival with hazard ratios of 0.51 (95% confidence interval 0.35 to 0.73, P < 0.001), 0.64 (95% confidence interval 0.43 to 0.96, P = 0.031) and 0.52 (95% confidence interval 0.28 to 0.97, P = 0.040), respectively, whereas pelvic nodal disease was associated with worse bRFS (hazard ratio 0.67, 95% confidence interval 0.46 to 0.98, P = 0.039) and MFS (hazard ratio 0.56, 95% confidence interval 0.37 to 0.85, P = 0.006). The acute and late radiation-related toxicities were low overall and pelvic nodal irradiation was associated with higher toxicities. CONCLUSION: Contemporary EBRT and long-term ADT led to excellent 5-year clinical outcomes and low rates of toxicity in this cohort of non-metastatic grade group 5 prostate cancers. Primary Gleason pattern 5 and pelvic node disease portends inferior clinical outcomes.

Exploring the Financial Toxicities of Patients with Locally Advanced Head and Neck Malignancies, Being Treated in a Private Sector Hospital in North India: A Thematic Analysis.

BACKGROUND: The high cost of cancer diagnosis and treatment is a global concern. Evidence derived, mostly from high-income countries, shows how it gradually impacts the personal and household financial condition causing the increased psychosocial burden of the patient and their families (termed "financial toxicity"). AIM: To qualitatively explore the financial toxicities in patients with advanced head and neck malignancies in India, and to consider how it impacts the patient and his family. METHODS: Interviewing a purposive sample of 8 patients using semi-structured interviews face to face. Interviews were transcribed verbatim, and a thematic content analysis was carried out. RESULTS: Four major themes were identified: burden and amplifying factors, impact, rescue and relieving factors, and learning and innovation. The burden of cost relates to diagnosis, treatment and non-medical costs which gets amplified while navigating the healthcare labyrinth. Emerging themes describe financial journey of cancer patients, the issues faced by them and the ways they tackle these issues during their treatment. Healthcare system factors like limited availability of adequate/comprehensive/meaningful insurance and reimbursements potentiate the toxicity. The financial toxicity leads to a significant adverse financial, psychological and social impact on the patient and the family. While moving through the process of care, there were a few learnings and innovations which patients proposed. CONCLUSION: This study provides qualitative evidence of the considerable and pervasive nature of financial toxicity in head and neck cancer patients in India. The findings have implications for all cancer patients and highlight the unmet need of psychosocial support for these patients.

Evolving multidisciplinary treatment of squamous cell carcinoma of the head and neck in India✰.

In this article, we highlight the evolution of a multimodal approach in the overall management of squamous cell carcinoma of the head and neck (SCCHN) in India; present advances in technology (newer surgical techniques), novel medical and radiotherapy (RT) approaches; review their roles for an integrated approach for treating SCCHN and discuss the current role of immunotherapy in SCCHN. For locally advanced (LA) SCCHN, the multidisciplinary approach includes surgery followed by RT, with or without chemotherapy (CT) or concurrent chemoradiotherapy. Improved surgical techniques of reconstruction and voice-preservation are being implemented. Advanced forms of high-precision conformal techniques like intensity-modulated radiotherapy are used to deliver highly conformal doses to tumors, sparing the surrounding normal tissue. Compared with RT alone, novel CT regimens and targeted therapeutic agents have the potential to improve locoregional control and survival and reduce treatment-induced toxicities. Several clinical trials have demonstrated efficacy, safety, and quality of life benefits of adding cetuximab to RT regimens in LASCCHN. Studies have also suggested a cetuximab-related laryngeal preservation benefit. At progression, platinum-based CT combined with cetuximab (a monoclonal anti-epidermal growth factor receptor antibody) is the only validated option available as the first-line therapy. Thus, an integrated multidisciplinary approach plays a key role in maximizing patient outcomes, reduction in treatment related morbidities that consequently impact quality of life of survivors.

Hypofractionated stereotactic body radiotherapy in spinal metastasis - with or without epidural extension.

AIMS: To evaluate clinical outcome and the effect of malignant epidural compression (MEC) in the treatment of spine metastasis with stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: Seventy-six lesions in 52 patients with spinal metastasis received SBRT during the period July 2010 to December 2012. MEC was detected in 20 patients (38.4%) and was separately contoured. The median dose prescribed to involved vertebra (planning target volume) was 24 Gy (range 24-27 Gy) in a median of three fractions (range 1-3). Uninvolved elements were prescribed 21 Gy in three fractions. In 59 lesions (77.6%), the entire vertebra was treated and in 17 lesions (22.4%) only the anterior elements were treated. All patients were treated with volumetric modulated arc therapy with image guidance on a Novalis Tx linear accelerator with the ExacTrac system. Dosimetric and clinical outcomes were compared in patients with or without MEC. RESULTS: At a median follow-up of 8.48 months (range 3-40 months), 1 year local control and overall survival was 94 and 68%, respectively. In patients with or without epidural extension, the median dose to the gross tumour volume (GTV; 95%) was 23.48 Gy (range 13.70-25.75) and 22.99 Gy (range 13.55-26.84), the median spinal cord Dmax was 17.36 Gy (range 8.47-21.63) and 15.71 Gy (range 8.39-23.33). The median GTV epidural (D95%) was 21.16 Gy (range 15.43-23.92). Complete pain relief was seen in 90% of patients with MEC and 93.75% without MEC (P=NS) and neurological improvement was seen in 60% of patients in both groups of patients. CONCLUSION: It is feasible to deliver a high dose of radiation (∼90% of the prescription dose) to the epidural component with volumetric modulated arc therapy SBRT and image guidance. It yielded high rates of pain control and local control in patients with spine metastases with or without MEC.

Consensus recommendations for management of head and neck cancer in Asian countries: a review of international guidelines.

Head and neck cancer (HNC) is a disease of the upper aerodigestive tract and is one of the most frequently diagnosed cancers worldwide. A high rate of cancers involving the head and neck are reported across the Asian region, with notable variations between countries. Disease prognosis is largely dependent on tumor stage and site. Patients with early stage disease have a 60-95% chance of cure with local therapy. Early diagnosis and appropriate treatment are important to increase the likelihood of cure and survival. However, the majority of patients present with locally advanced disease and require multimodality treatment. This necessitates, a multidisciplinary approach which is essential to make appropriate treatment decisions, particularly with regards to tolerability, costs, available infrastructure and quality of life issues. Unfortunately, majority of the studies that dictate current practice have been developed in the west where diseases biology, patient population and available infrastructure are very different from those in the Asian continent. With this in mind an expert panel of Head and Neck Oncologists was convened in May 2012 to review the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO) clinical practice guidelines and develop practical recommendations on the applicability of these guidelines on the management of head and neck cancer for Asian patients. The objective of this review and consensus meeting was to suggest revisions, to account for potential differences in demographics and resources, to the NCCN and ESMO guidelines, to better reflect current clinical management of head and neck cancer within the Asian region for health care providers. These recommendations, which reflect best clinical practice within Asia, are expected to benefit practitioners when making decisions regarding optimal treatment strategies for their patients.

Palliative weekly chemotherapy along with cetuximab in recurrent and metastatic head and neck cancers: a retrospective analysis.

BACKGROUND: This study was undertaken to report the results of weekly combination chemotherapy with cetuximab in recurrent/metastatic head and neck squamous cell carcinoma (R/M SCCHN). MATERIALS AND METHODS: Retrospective analysis of 35 R/M SCCHN patients who received cetuximab with weekly paclitaxel and platin (cisplatin/carboplatin) from SCCHN August 2006 to October 2008 at our Institute was performed. RESULTS: Thirty-five patients (33 [94.3%] males and 2 [5.7%] females) received the planned weekly chemotherapy protocol. Median age of these patients was 52 years. Of the SCCHN 32 evaluable patients, 25 patients showed symptomatic improvement and 7 showed no improvement. Radiological responses using RECIST criteria reported CR in 1 patient (3.1%), PR in 17 patients (53.1%), and SD in 6 patients (18.8%). The remaining six patients demonstrated disease progression while two could not be assessed. Median overall survival (OS) was 8.016 months (95% CI; 6.572--9.461) and median PFS was 5.782 months (95% CI; 4.521--7.044). The major chemotherapy-related grades 2 and 3 toxicity recorded was cetuximab-induced rash reported in 24 patients. No treatment-related death within 30 days was observed. CONCLUSION: Cetuximab with weekly combination chemotherapy (Paclitaxel + Platinum compound) has shown promise, demonstrating comparable response and outcomes with acceptable toxicity in R/M SCCHN patients.

Favourable impact of intensity-modulated radiation therapy on chronic dysphagia in patients with head and neck cancer.

The aim of this study was to evaluate the impact of intensity-modulated radiation therapy (IMRT) on the incidence and severity of chronic dysphagia in patients with head and neck cancer. 62 evaluable patients with head and neck cancer who were treated with IMRT with or without concurrent chemotherapy were analysed. The majority of the patients (77.4%) had advanced locoregional disease. 45 patients underwent definitive IMRT and 17 received post-operative IMRT. Concurrent chemotherapy was given to 29 of the 45 patients treated with definitive IMRT. The average prescribed dose to clinical target volume (CTV)1 was 66-70 Gy (definitive IMRT) and 56-62 Gy (post-operative IMRT); 60 Gy to CTV2; 54 Gy to CTV3; and 50-52 Gy to the supraclavicular area. At a median follow-up of 19 months, 2-year actuarial locoregional control and survival was 77% and 74%, respectively. At 6 months after IMRT, chronic dysphagia was Grade 0 in 77.1% of patients, Grade 1 in 10.5% and Grade 2 in 12.3%. Acute mucositis showed no correlation with long-term dysphagia. The percutaneous endoscopic gastrostomy or nasogastric tube was removed in all of the patients within 8 weeks of completion of treatment. Xerostomia was Grade 0 in 61.4% of patients, Grade 1 in 31.5% and Grade 2 in 7% of patients. In conclusion, IMRT conferred a major favourable impact on chronic dysphagia in patients with locally advanced head and neck cancers, with satisfactory locoregional control.

Isolated intraorbital metastasis in breast carcinoma.

We report a case of metastases to the eye, in a 30 year old lady with carcinoma breast leading to isolated metastatic involvement of the lateral rectus muscle with no evidence of metastases at any other site in the body after a follow up of one year after completion of chemotherapy.

Can dose reduction to one parotid gland prevent xerostomia?--A feasibility study for locally advanced head and neck cancer patients treated with intensity-modulated radiotherapy.

AIMS: Dryness of the mouth is one of the most distressing chronic toxicities of radiation therapy in head and neck cancers. In this study, parotid function was assessed in patients with locally advanced head and neck cancers undergoing intensity-modulated radiotherapy (IMRT) with or without chemotherapy. Parotid function was assessed with the help of a questionnaire and parotid scintigraphy, especially with regards to unilateral sparing of the parotid gland. MATERIALS AND METHODS: In total, 19 patients were treated with compensator-based IMRT between February 2003 and March 2004. The dose to the clinical target volume ranged between 66 and 70 Gy in 30-35 fractions to 95% of the isodose volume. Ipsilateral high-risk neck nodes received an average dose of 60 Gy and the contralateral low-risk neck received a dose of 54-56 Gy. Eight of 19 patients also received concomitant chemotherapy. RESULTS: Subjective toxicity to the parotid glands was assessed with the help of a questionnaire at 0, 3 and 6 months and objective toxicity was assessed with parotid scintigraphy at 0 and 3 months. The mean dose to the ipsilateral parotid gland ranged from 19.5 to 52.8 Gy (mean 33.14 Gy) and the mean dose to the contralateral gland was 11.1-46.6 Gy (mean 26.85 Gy). At a median follow-up of 13 months, 9/19 patients had no symptoms of dryness of the mouth (grade I), 8/19 had mild dryness of the mouth (grade II) and only 2/19 had grade III xerostomia, although the parotid gland could only be spared on one side in most of the patients. CONCLUSIONS: Minimising the radiation dose to one of the parotid glands with the help of IMRT in patients with advanced head and neck cancers can prevent xerostomia in most patients and parotid scintigraphy is a useful method of documenting xerostomia.

Impact of 6MV photon beam attenuation by carbon fiber couch and immobilization devices in IMRT planning and dose delivery.

Multiple fields in IMRT and optimization allow conformal dose to the target and reduced dose to the surroundings and the regions of interest. Thus we can escalate the dose to the target to achieve better tumor control with low morbidity. Orientation of multiple beams can be achieved by i) different gantry angles, ii) rotating patient's couch isocentrically. In doing so, one or more beam may pass through different materials like the treatment couch, immobilization cast fixation plate, head and neck rest or any other supportive device. Our observations for 6MV photon beam on PRIMUS-KXE2 with MED-TEC carbon fiber tabletop and 10 × 10 cm(2) field size reveals that the maximum dose attenuation by the couch was of the order of 2.96% from gantry angle 120-160°. Attenuation due to cast fixation base plate of PMMA alone was of the order of 5.8-10.55% at gantry angle between 0 and 90°. Attenuation due to carbon fiber base plate alone was 3.8-7.98%. Attenuation coefficient of carbon fiber and PMMA was evaluated and was of the order of 0.082 cm(-1) and 0.064 cm(-1) respectively. Most of the TPS are configured for direct beam incidence attenuation correction factors only. Whereas when the beam is obliquely incident on the couch, base plate, headrest and any other immobilization device get attenuated more than the direct beam incidence. The correction factors for oblique incidence beam attenuation are not configured in most of the commercially available treatment planning systems. Therefore, such high variations in dose delivery could lead to under-dosage to the target volume for treatments requiring multiple fields in IMRT and 3D-CRT and need to be corrected for monitor unit calculations.

Pericardial synovial sarcoma.

A 29-year-old young man presented with acute breathlessness. After investigative work-up he was found to have a massive pericardial tumour. Thoracotomy and near total surgical excision of the pericardial tumour was carried out. Histopathology and immunohistochemical markers study revealed it to be a synovial sarcoma arising from the left lateral pericardial surface. Postoperatively, he received external radiation and chemotherapy. Thirteen months after surgery he developed local recurrence which was unresectable.

Determination of cancer antigen 125 in ovarian carcinoma.

Appropriate therapeutic measures can improve the life expectancy of patients with ovarian malignancy. There has been a pressing need for serodiagnostic assays to enable, the close patient monitoring. Cancer Antigen 125 (CA125) has been described as a useful marker in patient monitoring for ovarian malignancy. Keeping this in view, the present study was planned. 40 consecutive female patients of ovarian carcinoma (mean age 52.4±10.7 years) were selected for serum CA125 analysis during the period of year 1995-2001. The tumour marker concentration was compared with histologic types of ovarian tumour and the FIGO staging of the disease. 25 healthy females (mean age 35.2-10.4 years) served as control. Mean serum CA125 concentrations in patients with papillary serous adenocarcinoma(Mean±%CV 1571±121.5 U/ml) was much higher than patients with mucinous adenocarcinoma(775±78U/ml). Mean serum CA125 concentration in endometrioid carcinoma was very high(2853±136 U/ml). The patient with clear cell carcinoma however had shown moderate increase(60 U/ml). No correlation was found between serum CA125 concentration and the FIGO staging of disease.Quantitation of CA125 was most helpful in monitoring the response of treatment and followup of the patients after completion of their treatment. Posttherapeutically its concentration showed more than 50% reduction in almost all (91.4%) patients (P<0.001). Importantly these patients had also shown significant regression of the disease clinically and radiologically. 8.6% of patients had shown static or increase in serum CA125 concentration which was associated with either clinically static or progressive disease. Recurrence of the disease was noted in patients who had shown increase in serum CA125 concentration (biochemical recurrence) in the followupHowever, in our test population biochemical recurrence(increase in serum marker concentration) preceded the clinical or radiological recurrence by an average of 6.5 months.Kaplan meier survival analysis for evaluation of overall survival in our test subjects showed an overall survival of 32% at one year and median survival of 9 months with confidence interval of 6.34 to 11.66. We conclude that serum CA125 is a useful marker for monitoring the treatment and predicting an early recurrence of the disease in ovarian carcinoma patients. A study in larger number of patients is needed to define its exact role in the management of the carcinoma ovary.

Vertebral haemangioma presenting as Kasabach-Merritt syndrome.

A case of spinal cord compression due to vertebral haemangioma is described as presenting as part of the Kasabach-Merritt syndrome, which is characterized by bleeding disorder, thrombocytopenia and leukopenia. A dramatic improvement in neurological status and coagulation profile following surgical decompression and postoperative radiotherapy is reported. A brief review of the literature on the usefulness of radiotherapy is discussed.

Anomalous lateral sulcus asymmetry and cognitive function in first-episode schizophrenia.

This study examines the cognitive functioning of first-episode schizophreniform patients within several weeks of hospitalization and at 2 years into the illness. Differences between patients and controls are also reported for measurements of the length of the lateral sulcus, which borders the planum temporal, an area of the brain integral to language function. Neuropsychological test results are also correlated to magnetic resonance imaging structural variables at the time of first hospitalization. Findings on neuropsychological summary scales reveal a diffuse pattern of cognitive impairment in schizophreniform patients compared to controls, which appears to improve over time. An atypical pattern of anatomic lateral symmetry is found in female schizophreniform patients, with female appearing to have a reduction in the normally occurring left greater than right length of the lateral sulcus. Such atypical asymmetry of the lateral sulcus is also associated with better cognitive function, particularly in schizophreniform patients. These findings suggest that atypical lateralization in an area critical to language function may be related to cognitive function in schizophreniform illness.

Selective embolization of internal iliac artery for massive haemorrhage from bladder secondary to carcinoma.

Uncontrolled haemorrhage from the urinary bladder secondary to carcinoma can at times be a life-threatening complication. We report a case of recurrent carcinoma of bladder where all the conservative measures for controlling hematuria had failed. Selective embolization of both internal iliac arteries was undertaken which controlled haematuria within 12 hours of the procedure. The procedure had not caused any complication up until the patient was last seen 5 months after the procedure.

Brain morphology in first-episode schizophrenic-like psychotic patients: a quantitative magnetic resonance imaging study.

Brain morphology was examined using magnetic resonance imaging in 30 first-episode patients with a schizophreniclike psychosis, 15 chronic schizophrenics, and 20 neurological controls. Statistical analyses of computer-generated measurements of regions of interest were controlled for gender, age, social class, and total brain volume. Lateral ventricular size was increased in both first-episode and chronic schizophrenic patients, with greater significance on the left than on the right side. Only the chronic patients, however, had reduced temporal lobe size, which also was greater on the left side. No major correlations of regional brain morphological measurements with cognitive functioning were found, although some measurements of verbal memory were correlated with parahippocampal size. This is a report of a preliminary study that suggests that some morphological brain changes may be present at the time of first treatment for a psychotic illness, whereas others may occur later in the course of illness. Future prospective studies may determine the clinical significance of these changes and whether they progress with the development of illness chronicity.