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Papers by Ziad Thotathil

Oncology Letters, Mar 26, 2024

Journal of Oncology, Oct 14, 2022

Background. Glioblastoma multiforme (GBM) may be susceptible to metabolic strategies such as fast... more Background. Glioblastoma multiforme (GBM) may be susceptible to metabolic strategies such as fasting and ketogenic diets, which lower blood glucose and elevate ketones. Combining these two strategies may be an ideal approach for sustaining a potentially therapeutic glucose ketone index (GKI). In this prospective case series, we observed whether a combined metabolic strategy was feasible, safe, and capable of sustaining a GKI <6 in patients with GBM. Methods. We provided recommendations and guidelines to 10 GBM patients at various stages of tumour progression and treatment that enabled them to complete a 5-7-day fast every 1-2 months combined with a modi ed ketogenic diet during the intervening weeks. Patients monitored their blood glucose and ketone levels and body weight. Adverse e ects were assessed. Results. Patients completed a mean of 161 ± 74 days of the combined metabolic strategy, with 34 ± 18 (21%) days of prolonged fasting (mean fast duration: 6.0 ± 1.4 days) and 127 ± 59 (79%) days on the ketogenic diet. e mean GKI for all 10 patients was 3.22 (1.28 during the fasts, 5.10 during the ketogenic diet). Body weight decreased by 8.4 ± 6.9 kg (11.2% decrease in baseline weight). e most common adverse e ects attributed to the fasts and ketogenic diet were fatigue, irritability, and feeling lightheaded. e metabolic strategy did not interfere with standard oncological treatments. Conclusion. is is the rst study to observe the feasibility and safety of repeated, prolonged fasting combined with a modi ed ketogenic diet in patients with GBM. Using minimal support, patients maintained the combined metabolic strategy for 5-6 months while sustaining a potentially therapeutic mean GKI of 3.22. Weight loss was considerable. Adverse e ects attributed to the metabolic strategy were mild, and it did not interfere with standard oncological treatments. Study Registration: is study is registered on the Australia New Zealand Clinical Trials Registry, number ACTRN12620001310954. e study was registered on 4 December 2020.

The New Zealand Medical Journal, Feb 5, 2021

AIM: Stereotactic ablative radiotherapy (SABR) involves the delivery of high doses of precisely t... more AIM: Stereotactic ablative radiotherapy (SABR) involves the delivery of high doses of precisely targeted radiation in a shorter time period than conventional radiotherapy. The aim of this study was to compare the outcomes of lung-based SABR in a New Zealand cohort to the global literature. METHODS: A single-institution retrospective analysis was performed on all patients who received lung-based SABR between May 2015 and September 2019 at Waikato Hospital, New Zealand. The study included both early stage lung cancer and lung oligometastases that measured less than 5cm. RESULTS: 102 patients received SABR to 116 lesions. Median follow-up was 19 months. The three-year rate of local control in the primary and metastatic cohorts was 85% and 82%, respectively. This reflects the three-year local control rate of 86% for primary lung cancer in the SPACE trial and the two-year local control rate of 81% for pulmonary oligometastases in a German study. Central primary lung cancer was associated with a higher risk of local recurrence (HR6.4 (1.3-31.5) p=0.02). The three-year progression-free survival rate in patients with early stage lung cancer and oligometastases was 56% and 26%, respectively. Māori patients with primary lung cancer had a significantly worse progression free survival (HR2.4 (1.1-5.1) p=0.03). There were no reported grade three toxicities. CONCLUSION: The use of lung-based SABR in a typical radiotherapy setting in New Zealand mirrors global outcomes.

Journal of Clinical Oncology, 2010

PURPOSE To investigate the feasibility of combining hyperfractionated radiotherapy regimen with c... more PURPOSE To investigate the feasibility of combining hyperfractionated radiotherapy regimen with concomitant chemotherapy and to assess its toxicity in patients with advanced head and neck carcinoma (HNC). Progression free survival (PFS) and overall survival (OS) were set as secondary end points. PATIENTS AND METHODS Between November 2003 and November 2007, 48 patients with stage III and IV HNC who met the eligibility criteria were enrolled in the study. Hyperfractionated Radiation consisted of 120 Gys twice daily, 6 hours apart, for a total of 69.6 Gys in 58 fractions over 6 weeks and boost of 6 Gys in 3 fractions in case of residual disease. Three cycles of concurrent chemotherapy in the form of Cisplatin 75 mg/ m² on day 1 and Fluorouracil 750 mg/m² 24 hour infusion on day 1-4 during weeks 1, 4 and 6 of irradiation. RESULTS 48 patients have completed the treatment to date. The median radiation dose was 72 Gys including the boost to residual lymph node or primary site. The treatment was delivered in a median overall period of 54 days, with a recorded median delay of 7 days. Grade 4 skin toxicity was experienced by 4.1% of patients only. Therapy was well tolerated (grade 3 mucositis in 21%, grade 4 in 26%, grade 3 leukopenia in 10%). Weight loss of more than 10 kg was reported in 10 (16.7%) of the cases. The most common late toxicity was mild to moderate xerostomia which was encountered in 34 (70.8%) cases and improved thereafter. Hypothyroidism was encountered in 7 (14.6%) of the cases. Complete response (CR) was observed in 40 patients (83.3%). Partial response (PR) was achieved in the remaining 8 patients (16.7%). Disease relapse occurred in 9 patients (18.8%) after complete response and 2 patients developed progressive disease after partial response. 3 patients relapsed locally, 5 patients developed distant metastasis and 1 patient developed both local and distant metastasis. 2 patients (4.1%) died of treatment complications, 8 patients (16.7%) died with progressive locoregional, and metastatic disease. The 2- year disease free survival was 77% and the 2- year overall survival was 79%. CONCLUSION Hyperfractionated radiotherapy and concurrent chemotherapy is tolerable. Results regarding LC and OS are encouraging as compared to conventional radiotherapy and concurrent chemotherapy.

AJNR. American journal of neuroradiology, 2018

In glioblastoma, tumor-associated macrophages have tumor-promoting properties. This study determi... more In glioblastoma, tumor-associated macrophages have tumor-promoting properties. This study determined whether routine MR imaging features could predict molecular subtypes of glioblastoma that differ in the content of tumor-associated macrophages. Seven internally derived MR imaging features were assessed in 180 patients, and 25 features from the Visually AcceSAble Rembrandt Images feature set were assessed in 164 patients. Glioblastomas were divided into subtypes based on the telomere maintenance mechanism: alternative lengthening of telomeres positive (ALT+) and negative (ALT-) and the content of tumor-associated macrophages (with [M+] or without [M-] a high content of macrophages). The 3 most frequent subtypes (ALT+/M-, ALT-/M+, and ALT-/M-) were correlated with MR imaging features and clinical parameters. The fourth group (ALT+/M+) did not have enough cases for correlation with MR imaging features. Tumors with a regular margin and those lacking a fungating margin, an expansive T1/...

International Journal of Molecular Sciences

The Δ133p53β isoform is increased in many primary tumors and has many tumor-promoting properties ... more The Δ133p53β isoform is increased in many primary tumors and has many tumor-promoting properties that contribute to increased proliferation, migration and inflammation. Here we investigated whether Δ133p53β contributed to some of the most aggressive tumors that had metastasized to the brain. Δ133p53β mRNA expression was measured in lung, breast, melanoma, colorectal metastases and, where available, the matched primary tumor. The presence of Δ133p53β expression was associated with the time for the primary tumor to metastasize and overall survival once the tumor was detected in the brain. Δ133p53β was present in over 50% of lung, breast, melanoma and colorectal metastases to the brain. It was also increased in the brain metastases compared with the matched primary tumor. Brain metastases with Δ133p53β expressed were associated with a reduced time for the primary tumor to metastasize to the brain compared with tumors with no Δ133p53β expression. In-vitro-based analyses in Δ133p53β-expr...

Medical and Pediatric Oncology, 2003

... Squamous carcinoma of the larynx and hypopharynx in children: A distinct clinical entity? Far... more ... Squamous carcinoma of the larynx and hypopharynx in children: A distinct clinical entity? Farzan Siddiqui DMRT, DNB 1 ,; Rajiv Sarin MD, DNB, FRCR 1,* ,; Jai Prakash Agarwal MD 1 ,; Ziad Thotathil MD, DNB 1 ,; Rajesh Mistry MS 2 ,; Ketayun A. Dinshaw DMRT, FRCR 1. ...

Medical Principles and Practice, 2004

Objectives: This retrospective study was undertaken to analyze the profile of patients presenting... more Objectives: This retrospective study was undertaken to analyze the profile of patients presenting with renal cell carcinoma (RCC) and treatment outcomes. Subjects and Methods: Records of 49 patients (36 male, 16 female, 21-75 years) treated at the Kuwait Cancer Control Center, Kuwait for RCC during the period 1993-1998 were analyzed. Forty-one patients had a nephrectomy, 18 postoperative radiotherapy and 1 patient also received adjuvant immunotherapy with interferon. Patients with metastatic disease were treated with a variety of agents including interferon, chemotherapy (vinblastine) or a hormonal agent (megestrol acetate). Data analysis was performed using SPSS statistical software package. Overall survival and disease-free survival were calculated using the Kaplan-Meier method. Results: Twenty-nine patients presented with symptoms classically associated with RCC. Metastases at diagnosis were seen in 9 patients (18%), with lung being the most frequent site. The commonest tumor subtype was clear cell carcinoma (32.6%). Thirtynine patients (80%) achieved a complete response to treatment and relapse was documented in 10 patients (26%). The majority of failures were distant, with lung metastases being the most common. Response to salvage treatment was poor. Overall survival was 83% at 2 years. The disease-free survival was 68 and 45% at 2 and 5 years, respectively. Conclusions: Although many patients presented with advanced local disease, a majority achieved complete response after radical surgery with or without postoperative radiation therapy. Salvage of metastatic disease proved difficult with interferon, chemotherapy.

Medical Principles and Practice, 2004

Objective: Primary tumors of the trachea are extremely rare. Treatment methods vary considerably ... more Objective: Primary tumors of the trachea are extremely rare. Treatment methods vary considerably and few studies have sought to provide adequate guidelines. This study reviews the records of patients treated for tracheal cancer at the Tata Memorial Hospital (TMH), Mumbai, India. Subjects and Methods: Fifteen patients with primary tracheal malignancies were identified in the TMH database during the period from 1983 to 2000. They were predominantly males (87%) belonging to an older age-group (67% above 40 years). Common presenting symptoms were cough, hoarseness, hemoptysis and indications of airway obstruction. Squamous cell carcinoma was the commonest histologic subtype (40%) followed by adenoid cystic carcinoma (27%). Ten patients received radical treatment. One patient underwent surgery (resection and anastomosis) and received postoperative radiotherapy. Another was explored but was found to be unresectable and was 1 of 2 patients treated with chemotherapy and radiotherapy. Laser resections and radiotherapy were used in 2 patients while 4 patients were managed with radiotherapy alone. One patient was treated elsewhere. The majority of patients (8/9) were treated with locoregional fields and doses ranging from 40 to 60 Gy (median 50 Gy). Two patients also received intraluminal brachytherapy, 1 as part of initial treatment and another for recurrence. Results: Only 5 patients treated at TMH (5/9) achieved local control of their disease. Follow-up times ranged from 1 month to 134 months, median of 38 months. Distant metastases were identified in 4 patients (bone n = 1 and lung n = 3). Median survival was 38 months. Overall survival at 5 years was 37% by Kaplan-Meier method, but this figure should be treated with caution since only 6 patients had a follow-up of more than 2 years. Conclusion: Tracheal cancer is a rare malignancy. Radiation therapy is a reasonably effective modality for unresectable disease.

Medical Principles and Practice, 2006

Materials and Methods From January 1993 to 1998, 823 consecutive patients with primary breast can... more Materials and Methods From January 1993 to 1998, 823 consecutive patients with primary breast cancer had surgery and subsequent therapy at Kuwait Cancer Control Center. Thirty-eight files were excluded from the analysis because of inadequate information, leaving 785 files for further analysis. All patients were clinically staged by physical

Journal of Thoracic Oncology, 2007

Bronchorrhea is described as a rare complication of bronchoalveolar carcinoma. 1 Here, we describ... more Bronchorrhea is described as a rare complication of bronchoalveolar carcinoma. 1 Here, we describe the treatment of this condition with erlotinib, an EGFR tyrosine kinase inhibitor. Our patient was a 59-year-old man with a 40pack-year history, who presented with a relatively short, 2-week history of cough with expectoration and shortness of breath. A computed tomography scan showed diffuse infiltrative changes involving the right lung but also a right hilar mass, mediastinal lymphadenopathy, and a mass in the adrenal suggestive of metastases. There was no intrabronchial tumor on bronchoscopy, and biopsy only revealed areas of dysplasia without invasion. The cytology report indicated a non-small cell carcinoma. The clinical and radiological features were consistent with bronchoalveolar carcinoma. 2 He received a cycle of cisplatinum and gemcitabine chemotherapy, but he presented a week later, severely short of breath and complaining of a copious expectorate amounting to more than 2 liters/day of mucoid sputum. We tried antibiotics, amitryptiline and hyoscine hydrobromide cutaneous patch, octreotide and hyoscine butylbromide subcutaneous infusions, and steroid both locally (beclomethasone inhaler) and systemically (dexamethasone), without any significant benefit. Noting case reports describing response of bronchorrhea to gefitinib, 3 we offered him erlotinib because we had access to the drug on an expanded access program.

Expert Opinion on Investigational Drugs, 2007

Immunotherapy involves the treatment of cancer by modification of the host-tumour relationship. I... more Immunotherapy involves the treatment of cancer by modification of the host-tumour relationship. It is now known that this relationship is quite complex and only some of the interactions have been elucidated. Early attempts at immunotherapy, such as Coley&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s toxins, were undertaken without an understanding of the processes mediating the effects. With a better understanding of the immunology of this anticancer response, recent trials have focussed on certain aspects of the process to stimulate an antitumour response. In this review, the authors discuss a number of novel biological response modifiers that work as general stimulants of the immune system, through varied mechanisms including induction of stimulatory cytokines (such as IFN-alpha, TNF-alpha and IL-12) and activation of T cells and the antigen-presenting dendritic cells. These compounds include Toll-like receptor agonists, several of which are in clinical trials at present. In addition to immunomodulatory activity, some compounds such as 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and thalidomide and its analogues also target existing or developing tumour vasculature. Some of these compounds have single-agent activity in clinical trials, while others such as DMXAA have shown promise in combination with chemotherapy without increasing toxicity. Lactoferrin is another compound that has shown clinical activity with low toxicity. At present, accepted indications for immunotherapy are limited to a few cancers such as renal cell carcinoma and melanoma. This paper looks at some of the reasons for the limited impact of immunotherapy so far and suggest possible avenues for further research with a greater likelihood of success.

The Lancet. Oncology, Oct 22, 2017

Rindopepimut (also known as CDX-110), a vaccine targeting the EGFR deletion mutation EGFRvIII, co... more Rindopepimut (also known as CDX-110), a vaccine targeting the EGFR deletion mutation EGFRvIII, consists of an EGFRvIII-specific peptide conjugated to keyhole limpet haemocyanin. In the ACT IV study, we aimed to assess whether or not the addition of rindopepimut to standard chemotherapy is able to improve survival in patients with EGFRvIII-positive glioblastoma. In this randomised, double-blind, phase 3 trial, we recruited patients aged 18 years and older with glioblastoma from 165 hospitals in 22 countries. Eligible patients had newly diagnosed glioblastoma confirmed to express EGFRvIII by central analysis, and had undergone maximal surgical resection and completion of standard chemoradiation without progression. Patients were stratified by European Organisation for Research and Treatment of Cancer recursive partitioning analysis class, MGMT promoter methylation, and geographical region, and randomly assigned (1:1) with a prespecified randomisation sequence (block size of four) to r...

New Zealand medical journal (Print), Jul 20, 2007

Colorectal cancer is the second most common site of cancer for both men and women in New Zealand ... more Colorectal cancer is the second most common site of cancer for both men and women in New Zealand (NZ). Survival, especially with metastatic disease, has improved considerably over the last decade with the introduction of new chemotherapeutic agents. A questionnaire-based survey was conducted to document variations in chemotherapy prescription patterns throughout NZ. Out of 25 medical oncologists, responses were obtained from 22 (88%). The patient with stage III colon cancer was offered either 5-fluorouracil/leucovorin, most commonly on the weekly bolus schedule, or capecitabine monotherapy. Chemotherapy was also offered by the majority (65%) of respondents to the patient with 'high-risk' stage II colon cancer. Several chemotherapy combinations are available in NZ in the metastatic setting, with the most popular being oxaliplatin/capecitabine combination (CAPOX) (35%) or irinotecan/5-FU combination (FOLFIRI) (23%). None of the respondents would commence chemotherapy solely on...

Poster: "RANZCR FRO 2012 / RO-0029 / Outcomes after radical IMRT for head and neck cancer&qu... more Poster: "RANZCR FRO 2012 / RO-0029 / Outcomes after radical IMRT for head and neck cancer" by: "Z. Thotathil, S. Joseph, M. Tills, C. Hartopeanu, C. de Groot, K. Grimshaw, T. Cameron; Waikato/NZ"

Poster: "RANZCR FRO 2012 / RO-0031 / Radical radiotherapy with/without chemotherapy for NSCL... more Poster: "RANZCR FRO 2012 / RO-0031 / Radical radiotherapy with/without chemotherapy for NSCLC: a retrospective review" by: "Z. Thotathil, J. Chin; Waikato/NZ"

The New Zealand medical journal, 2007

Colorectal cancer is the second most common site of cancer for both men and women in New Zealand ... more Colorectal cancer is the second most common site of cancer for both men and women in New Zealand (NZ). Survival, especially with metastatic disease, has improved considerably over the last decade with the introduction of new chemotherapeutic agents. A questionnaire-based survey was conducted to document variations in chemotherapy prescription patterns throughout NZ. Out of 25 medical oncologists, responses were obtained from 22 (88%). The patient with stage III colon cancer was offered either 5-fluorouracil/leucovorin, most commonly on the weekly bolus schedule, or capecitabine monotherapy. Chemotherapy was also offered by the majority (65%) of respondents to the patient with 'high-risk' stage II colon cancer. Several chemotherapy combinations are available in NZ in the metastatic setting, with the most popular being oxaliplatin/capecitabine combination (CAPOX) (35%) or irinotecan/5-FU combination (FOLFIRI) (23%). None of the respondents would commence chemotherapy solely on...

Poster: "2019 ASM / R-0112 / Effectiveness of radiotherapy for Thyroid eye disease" by:... more Poster: "2019 ASM / R-0112 / Effectiveness of radiotherapy for Thyroid eye disease" by: "E. Isdale, Z. Thotathil; Hamilton/NZ"

Poster: "RANZCR ASM 2011 / R-0172 / IMRT Reporting Using ICRU Report 83 Criteria: A Retrospe... more Poster: "RANZCR ASM 2011 / R-0172 / IMRT Reporting Using ICRU Report 83 Criteria: A Retrospective Analysis" by: "Z. Thotathil, K. Grimshaw, T. Cameron; Hamilton/NZ"

Oncology Letters, Mar 26, 2024

Journal of Oncology, Oct 14, 2022

Background. Glioblastoma multiforme (GBM) may be susceptible to metabolic strategies such as fast... more Background. Glioblastoma multiforme (GBM) may be susceptible to metabolic strategies such as fasting and ketogenic diets, which lower blood glucose and elevate ketones. Combining these two strategies may be an ideal approach for sustaining a potentially therapeutic glucose ketone index (GKI). In this prospective case series, we observed whether a combined metabolic strategy was feasible, safe, and capable of sustaining a GKI <6 in patients with GBM. Methods. We provided recommendations and guidelines to 10 GBM patients at various stages of tumour progression and treatment that enabled them to complete a 5-7-day fast every 1-2 months combined with a modi ed ketogenic diet during the intervening weeks. Patients monitored their blood glucose and ketone levels and body weight. Adverse e ects were assessed. Results. Patients completed a mean of 161 ± 74 days of the combined metabolic strategy, with 34 ± 18 (21%) days of prolonged fasting (mean fast duration: 6.0 ± 1.4 days) and 127 ± 59 (79%) days on the ketogenic diet. e mean GKI for all 10 patients was 3.22 (1.28 during the fasts, 5.10 during the ketogenic diet). Body weight decreased by 8.4 ± 6.9 kg (11.2% decrease in baseline weight). e most common adverse e ects attributed to the fasts and ketogenic diet were fatigue, irritability, and feeling lightheaded. e metabolic strategy did not interfere with standard oncological treatments. Conclusion. is is the rst study to observe the feasibility and safety of repeated, prolonged fasting combined with a modi ed ketogenic diet in patients with GBM. Using minimal support, patients maintained the combined metabolic strategy for 5-6 months while sustaining a potentially therapeutic mean GKI of 3.22. Weight loss was considerable. Adverse e ects attributed to the metabolic strategy were mild, and it did not interfere with standard oncological treatments. Study Registration: is study is registered on the Australia New Zealand Clinical Trials Registry, number ACTRN12620001310954. e study was registered on 4 December 2020.

The New Zealand Medical Journal, Feb 5, 2021

AIM: Stereotactic ablative radiotherapy (SABR) involves the delivery of high doses of precisely t... more AIM: Stereotactic ablative radiotherapy (SABR) involves the delivery of high doses of precisely targeted radiation in a shorter time period than conventional radiotherapy. The aim of this study was to compare the outcomes of lung-based SABR in a New Zealand cohort to the global literature. METHODS: A single-institution retrospective analysis was performed on all patients who received lung-based SABR between May 2015 and September 2019 at Waikato Hospital, New Zealand. The study included both early stage lung cancer and lung oligometastases that measured less than 5cm. RESULTS: 102 patients received SABR to 116 lesions. Median follow-up was 19 months. The three-year rate of local control in the primary and metastatic cohorts was 85% and 82%, respectively. This reflects the three-year local control rate of 86% for primary lung cancer in the SPACE trial and the two-year local control rate of 81% for pulmonary oligometastases in a German study. Central primary lung cancer was associated with a higher risk of local recurrence (HR6.4 (1.3-31.5) p=0.02). The three-year progression-free survival rate in patients with early stage lung cancer and oligometastases was 56% and 26%, respectively. Māori patients with primary lung cancer had a significantly worse progression free survival (HR2.4 (1.1-5.1) p=0.03). There were no reported grade three toxicities. CONCLUSION: The use of lung-based SABR in a typical radiotherapy setting in New Zealand mirrors global outcomes.

Journal of Clinical Oncology, 2010

PURPOSE To investigate the feasibility of combining hyperfractionated radiotherapy regimen with c... more PURPOSE To investigate the feasibility of combining hyperfractionated radiotherapy regimen with concomitant chemotherapy and to assess its toxicity in patients with advanced head and neck carcinoma (HNC). Progression free survival (PFS) and overall survival (OS) were set as secondary end points. PATIENTS AND METHODS Between November 2003 and November 2007, 48 patients with stage III and IV HNC who met the eligibility criteria were enrolled in the study. Hyperfractionated Radiation consisted of 120 Gys twice daily, 6 hours apart, for a total of 69.6 Gys in 58 fractions over 6 weeks and boost of 6 Gys in 3 fractions in case of residual disease. Three cycles of concurrent chemotherapy in the form of Cisplatin 75 mg/ m² on day 1 and Fluorouracil 750 mg/m² 24 hour infusion on day 1-4 during weeks 1, 4 and 6 of irradiation. RESULTS 48 patients have completed the treatment to date. The median radiation dose was 72 Gys including the boost to residual lymph node or primary site. The treatment was delivered in a median overall period of 54 days, with a recorded median delay of 7 days. Grade 4 skin toxicity was experienced by 4.1% of patients only. Therapy was well tolerated (grade 3 mucositis in 21%, grade 4 in 26%, grade 3 leukopenia in 10%). Weight loss of more than 10 kg was reported in 10 (16.7%) of the cases. The most common late toxicity was mild to moderate xerostomia which was encountered in 34 (70.8%) cases and improved thereafter. Hypothyroidism was encountered in 7 (14.6%) of the cases. Complete response (CR) was observed in 40 patients (83.3%). Partial response (PR) was achieved in the remaining 8 patients (16.7%). Disease relapse occurred in 9 patients (18.8%) after complete response and 2 patients developed progressive disease after partial response. 3 patients relapsed locally, 5 patients developed distant metastasis and 1 patient developed both local and distant metastasis. 2 patients (4.1%) died of treatment complications, 8 patients (16.7%) died with progressive locoregional, and metastatic disease. The 2- year disease free survival was 77% and the 2- year overall survival was 79%. CONCLUSION Hyperfractionated radiotherapy and concurrent chemotherapy is tolerable. Results regarding LC and OS are encouraging as compared to conventional radiotherapy and concurrent chemotherapy.

AJNR. American journal of neuroradiology, 2018

In glioblastoma, tumor-associated macrophages have tumor-promoting properties. This study determi... more In glioblastoma, tumor-associated macrophages have tumor-promoting properties. This study determined whether routine MR imaging features could predict molecular subtypes of glioblastoma that differ in the content of tumor-associated macrophages. Seven internally derived MR imaging features were assessed in 180 patients, and 25 features from the Visually AcceSAble Rembrandt Images feature set were assessed in 164 patients. Glioblastomas were divided into subtypes based on the telomere maintenance mechanism: alternative lengthening of telomeres positive (ALT+) and negative (ALT-) and the content of tumor-associated macrophages (with [M+] or without [M-] a high content of macrophages). The 3 most frequent subtypes (ALT+/M-, ALT-/M+, and ALT-/M-) were correlated with MR imaging features and clinical parameters. The fourth group (ALT+/M+) did not have enough cases for correlation with MR imaging features. Tumors with a regular margin and those lacking a fungating margin, an expansive T1/...

International Journal of Molecular Sciences

The Δ133p53β isoform is increased in many primary tumors and has many tumor-promoting properties ... more The Δ133p53β isoform is increased in many primary tumors and has many tumor-promoting properties that contribute to increased proliferation, migration and inflammation. Here we investigated whether Δ133p53β contributed to some of the most aggressive tumors that had metastasized to the brain. Δ133p53β mRNA expression was measured in lung, breast, melanoma, colorectal metastases and, where available, the matched primary tumor. The presence of Δ133p53β expression was associated with the time for the primary tumor to metastasize and overall survival once the tumor was detected in the brain. Δ133p53β was present in over 50% of lung, breast, melanoma and colorectal metastases to the brain. It was also increased in the brain metastases compared with the matched primary tumor. Brain metastases with Δ133p53β expressed were associated with a reduced time for the primary tumor to metastasize to the brain compared with tumors with no Δ133p53β expression. In-vitro-based analyses in Δ133p53β-expr...

Medical and Pediatric Oncology, 2003

... Squamous carcinoma of the larynx and hypopharynx in children: A distinct clinical entity? Far... more ... Squamous carcinoma of the larynx and hypopharynx in children: A distinct clinical entity? Farzan Siddiqui DMRT, DNB 1 ,; Rajiv Sarin MD, DNB, FRCR 1,* ,; Jai Prakash Agarwal MD 1 ,; Ziad Thotathil MD, DNB 1 ,; Rajesh Mistry MS 2 ,; Ketayun A. Dinshaw DMRT, FRCR 1. ...

Medical Principles and Practice, 2004

Objectives: This retrospective study was undertaken to analyze the profile of patients presenting... more Objectives: This retrospective study was undertaken to analyze the profile of patients presenting with renal cell carcinoma (RCC) and treatment outcomes. Subjects and Methods: Records of 49 patients (36 male, 16 female, 21-75 years) treated at the Kuwait Cancer Control Center, Kuwait for RCC during the period 1993-1998 were analyzed. Forty-one patients had a nephrectomy, 18 postoperative radiotherapy and 1 patient also received adjuvant immunotherapy with interferon. Patients with metastatic disease were treated with a variety of agents including interferon, chemotherapy (vinblastine) or a hormonal agent (megestrol acetate). Data analysis was performed using SPSS statistical software package. Overall survival and disease-free survival were calculated using the Kaplan-Meier method. Results: Twenty-nine patients presented with symptoms classically associated with RCC. Metastases at diagnosis were seen in 9 patients (18%), with lung being the most frequent site. The commonest tumor subtype was clear cell carcinoma (32.6%). Thirtynine patients (80%) achieved a complete response to treatment and relapse was documented in 10 patients (26%). The majority of failures were distant, with lung metastases being the most common. Response to salvage treatment was poor. Overall survival was 83% at 2 years. The disease-free survival was 68 and 45% at 2 and 5 years, respectively. Conclusions: Although many patients presented with advanced local disease, a majority achieved complete response after radical surgery with or without postoperative radiation therapy. Salvage of metastatic disease proved difficult with interferon, chemotherapy.

Medical Principles and Practice, 2004

Objective: Primary tumors of the trachea are extremely rare. Treatment methods vary considerably ... more Objective: Primary tumors of the trachea are extremely rare. Treatment methods vary considerably and few studies have sought to provide adequate guidelines. This study reviews the records of patients treated for tracheal cancer at the Tata Memorial Hospital (TMH), Mumbai, India. Subjects and Methods: Fifteen patients with primary tracheal malignancies were identified in the TMH database during the period from 1983 to 2000. They were predominantly males (87%) belonging to an older age-group (67% above 40 years). Common presenting symptoms were cough, hoarseness, hemoptysis and indications of airway obstruction. Squamous cell carcinoma was the commonest histologic subtype (40%) followed by adenoid cystic carcinoma (27%). Ten patients received radical treatment. One patient underwent surgery (resection and anastomosis) and received postoperative radiotherapy. Another was explored but was found to be unresectable and was 1 of 2 patients treated with chemotherapy and radiotherapy. Laser resections and radiotherapy were used in 2 patients while 4 patients were managed with radiotherapy alone. One patient was treated elsewhere. The majority of patients (8/9) were treated with locoregional fields and doses ranging from 40 to 60 Gy (median 50 Gy). Two patients also received intraluminal brachytherapy, 1 as part of initial treatment and another for recurrence. Results: Only 5 patients treated at TMH (5/9) achieved local control of their disease. Follow-up times ranged from 1 month to 134 months, median of 38 months. Distant metastases were identified in 4 patients (bone n = 1 and lung n = 3). Median survival was 38 months. Overall survival at 5 years was 37% by Kaplan-Meier method, but this figure should be treated with caution since only 6 patients had a follow-up of more than 2 years. Conclusion: Tracheal cancer is a rare malignancy. Radiation therapy is a reasonably effective modality for unresectable disease.

Medical Principles and Practice, 2006

Materials and Methods From January 1993 to 1998, 823 consecutive patients with primary breast can... more Materials and Methods From January 1993 to 1998, 823 consecutive patients with primary breast cancer had surgery and subsequent therapy at Kuwait Cancer Control Center. Thirty-eight files were excluded from the analysis because of inadequate information, leaving 785 files for further analysis. All patients were clinically staged by physical

Journal of Thoracic Oncology, 2007

Bronchorrhea is described as a rare complication of bronchoalveolar carcinoma. 1 Here, we describ... more Bronchorrhea is described as a rare complication of bronchoalveolar carcinoma. 1 Here, we describe the treatment of this condition with erlotinib, an EGFR tyrosine kinase inhibitor. Our patient was a 59-year-old man with a 40pack-year history, who presented with a relatively short, 2-week history of cough with expectoration and shortness of breath. A computed tomography scan showed diffuse infiltrative changes involving the right lung but also a right hilar mass, mediastinal lymphadenopathy, and a mass in the adrenal suggestive of metastases. There was no intrabronchial tumor on bronchoscopy, and biopsy only revealed areas of dysplasia without invasion. The cytology report indicated a non-small cell carcinoma. The clinical and radiological features were consistent with bronchoalveolar carcinoma. 2 He received a cycle of cisplatinum and gemcitabine chemotherapy, but he presented a week later, severely short of breath and complaining of a copious expectorate amounting to more than 2 liters/day of mucoid sputum. We tried antibiotics, amitryptiline and hyoscine hydrobromide cutaneous patch, octreotide and hyoscine butylbromide subcutaneous infusions, and steroid both locally (beclomethasone inhaler) and systemically (dexamethasone), without any significant benefit. Noting case reports describing response of bronchorrhea to gefitinib, 3 we offered him erlotinib because we had access to the drug on an expanded access program.

Expert Opinion on Investigational Drugs, 2007

Immunotherapy involves the treatment of cancer by modification of the host-tumour relationship. I... more Immunotherapy involves the treatment of cancer by modification of the host-tumour relationship. It is now known that this relationship is quite complex and only some of the interactions have been elucidated. Early attempts at immunotherapy, such as Coley&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s toxins, were undertaken without an understanding of the processes mediating the effects. With a better understanding of the immunology of this anticancer response, recent trials have focussed on certain aspects of the process to stimulate an antitumour response. In this review, the authors discuss a number of novel biological response modifiers that work as general stimulants of the immune system, through varied mechanisms including induction of stimulatory cytokines (such as IFN-alpha, TNF-alpha and IL-12) and activation of T cells and the antigen-presenting dendritic cells. These compounds include Toll-like receptor agonists, several of which are in clinical trials at present. In addition to immunomodulatory activity, some compounds such as 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and thalidomide and its analogues also target existing or developing tumour vasculature. Some of these compounds have single-agent activity in clinical trials, while others such as DMXAA have shown promise in combination with chemotherapy without increasing toxicity. Lactoferrin is another compound that has shown clinical activity with low toxicity. At present, accepted indications for immunotherapy are limited to a few cancers such as renal cell carcinoma and melanoma. This paper looks at some of the reasons for the limited impact of immunotherapy so far and suggest possible avenues for further research with a greater likelihood of success.

The Lancet. Oncology, Oct 22, 2017

Rindopepimut (also known as CDX-110), a vaccine targeting the EGFR deletion mutation EGFRvIII, co... more Rindopepimut (also known as CDX-110), a vaccine targeting the EGFR deletion mutation EGFRvIII, consists of an EGFRvIII-specific peptide conjugated to keyhole limpet haemocyanin. In the ACT IV study, we aimed to assess whether or not the addition of rindopepimut to standard chemotherapy is able to improve survival in patients with EGFRvIII-positive glioblastoma. In this randomised, double-blind, phase 3 trial, we recruited patients aged 18 years and older with glioblastoma from 165 hospitals in 22 countries. Eligible patients had newly diagnosed glioblastoma confirmed to express EGFRvIII by central analysis, and had undergone maximal surgical resection and completion of standard chemoradiation without progression. Patients were stratified by European Organisation for Research and Treatment of Cancer recursive partitioning analysis class, MGMT promoter methylation, and geographical region, and randomly assigned (1:1) with a prespecified randomisation sequence (block size of four) to r...

New Zealand medical journal (Print), Jul 20, 2007

Colorectal cancer is the second most common site of cancer for both men and women in New Zealand ... more Colorectal cancer is the second most common site of cancer for both men and women in New Zealand (NZ). Survival, especially with metastatic disease, has improved considerably over the last decade with the introduction of new chemotherapeutic agents. A questionnaire-based survey was conducted to document variations in chemotherapy prescription patterns throughout NZ. Out of 25 medical oncologists, responses were obtained from 22 (88%). The patient with stage III colon cancer was offered either 5-fluorouracil/leucovorin, most commonly on the weekly bolus schedule, or capecitabine monotherapy. Chemotherapy was also offered by the majority (65%) of respondents to the patient with 'high-risk' stage II colon cancer. Several chemotherapy combinations are available in NZ in the metastatic setting, with the most popular being oxaliplatin/capecitabine combination (CAPOX) (35%) or irinotecan/5-FU combination (FOLFIRI) (23%). None of the respondents would commence chemotherapy solely on...

Poster: "RANZCR FRO 2012 / RO-0029 / Outcomes after radical IMRT for head and neck cancer&qu... more Poster: "RANZCR FRO 2012 / RO-0029 / Outcomes after radical IMRT for head and neck cancer" by: "Z. Thotathil, S. Joseph, M. Tills, C. Hartopeanu, C. de Groot, K. Grimshaw, T. Cameron; Waikato/NZ"

Poster: "RANZCR FRO 2012 / RO-0031 / Radical radiotherapy with/without chemotherapy for NSCL... more Poster: "RANZCR FRO 2012 / RO-0031 / Radical radiotherapy with/without chemotherapy for NSCLC: a retrospective review" by: "Z. Thotathil, J. Chin; Waikato/NZ"

The New Zealand medical journal, 2007

Colorectal cancer is the second most common site of cancer for both men and women in New Zealand ... more Colorectal cancer is the second most common site of cancer for both men and women in New Zealand (NZ). Survival, especially with metastatic disease, has improved considerably over the last decade with the introduction of new chemotherapeutic agents. A questionnaire-based survey was conducted to document variations in chemotherapy prescription patterns throughout NZ. Out of 25 medical oncologists, responses were obtained from 22 (88%). The patient with stage III colon cancer was offered either 5-fluorouracil/leucovorin, most commonly on the weekly bolus schedule, or capecitabine monotherapy. Chemotherapy was also offered by the majority (65%) of respondents to the patient with 'high-risk' stage II colon cancer. Several chemotherapy combinations are available in NZ in the metastatic setting, with the most popular being oxaliplatin/capecitabine combination (CAPOX) (35%) or irinotecan/5-FU combination (FOLFIRI) (23%). None of the respondents would commence chemotherapy solely on...

Poster: "2019 ASM / R-0112 / Effectiveness of radiotherapy for Thyroid eye disease" by:... more Poster: "2019 ASM / R-0112 / Effectiveness of radiotherapy for Thyroid eye disease" by: "E. Isdale, Z. Thotathil; Hamilton/NZ"

Poster: "RANZCR ASM 2011 / R-0172 / IMRT Reporting Using ICRU Report 83 Criteria: A Retrospe... more Poster: "RANZCR ASM 2011 / R-0172 / IMRT Reporting Using ICRU Report 83 Criteria: A Retrospective Analysis" by: "Z. Thotathil, K. Grimshaw, T. Cameron; Hamilton/NZ"