A pilot phase Ib/II study of whole-lung low dose radiation therapy (LDRT) for the treatment of severe COVID-19 pneumonia: First experience from Africa.

BACKGROUND: Low dose radiation therapy (LDRT) has been used for non-malignant conditions since early 1900s based on the ability of single fractions between 50-150 cGy to inhibit cellular proliferation. Given scarcity of resources, poor access to vaccines and medical therapies within low and middle income countries, there is an urgent need to identify other cost-effective alternatives in management of COVID-19 pneumonia. We conducted a pilot phase Ib/II investigator-initiated clinical trial to assess the safety, feasibility, and toxicity of LDRT in patients with severe COVID-19 pneumonia at the Aga Khan University Hospital in Nairobi, Kenya. Additionally, we also assessed clinical benefit in terms of improvement in oxygenation at day 3 following LDRT and the ability to avoid mechanical ventilation at day 7 post LDRT. METHODS: Patients with both polymerase chain reaction (PCR) and high-resolution computer tomogram (HRCT) confirmed severe COVID-19 pneumonia, not improving on conventional therapy including Dexamethasone and with increasing oxygen requirement were enrolled in the study. Patients on mechanical ventilation were excluded. Eligible patients received a single 100cGy fraction to the whole lung. In the absence of any dose limiting toxicity the study proposed to treat a total of 10 patients. The primary endpoints were to assess the safety/feasibility, and toxicity within the first 24 hours post LDRT. The secondary endpoints were to assess efficacy of LDRT at Day 3, 7, 14 and 28 post LDRT. RESULTS: Ten patients were treated with LDRT. All (100%) of patients were able to complete LDRT without treatment related SAE within the first 24 hours post treatment. None of the patients treated with LDRT experienced any acute toxicity as defined by change in clinical and respiratory status at 24hr following LDRT. Majority (90%) of patients avoided mechanical ventilation within 7 days of LDRT. Four patients (40%) demonstrated at least 25% improvement in oxygen requirements within 3 days. Six patients (60%) were discharged and remained off oxygen, whereas four progressed and died (1 due to sepsis and 3 in cytokine storm). Median time to discharge (n = 6) was 16.5 days and median time to death (n = 4) was 11.0 days. Patients who ultimately died showed elevated inflammatory markers including Ferritin, CRP and D-dimers as compared to those who were discharged alive. CONCLUSION: LDRT was feasible, safe and shows promise in the management of severe COVID-19 pneumonia including in patients progressing on conventional systemic treatment. Additional phase II trials are warranted to identify patients most likely to benefit from LDRT.

Managing soft tissue sarcomas in a developing country: are prognostic factors similar to those of developed world?

BACKGROUND: Managing soft tissue sarcomas (STS) in a developing country with limited financial resources and a poor health referral system is a challenge. Presenting late, these extremity STS are prone to recurrence despite apparently complete resection. This study aimed to explore and compare the impact of clinico-pathological factors on recurrence and survival in Pakistan with the corresponding figures quoted from the developed world. METHODS: An institutional review was performed on all patients with primary STS of the extremities operated on between 1994 and 2008. The prognostic influence of clinical, pathologic, and treatment variables on local recurrence free survival (LRFS), metastasis free survival (MFS) and overall survival (OS) were analyzed by univariate and multivariate Cox regression analysis and Kaplan Meier survival curves. RESULTS: A total of 84 patients with a mean age of 41.8 ± 21.9 years were included in the study. The local recurrence rate was 14.3% after a median of 6 (mean 7.4) months. Metastases occurred in 7 patients (8.3%) and 65 patients were alive without evidence of disease after a mean follow-up of 52.6 ± 39.8 months. Tumor size > 5 cm, grade 3 tumors and margin < 10 mm significantly increased local recurrence rates. A margin ≥ 10 mm and age < 45 years significantly enhanced cumulative survival. Significant multivariate risk factors for metastases were margin < 10 mm and tumor grade G3. CONCLUSIONS: Despite a poor health referral system in our country, our results are no different from those reported from the developed world. Surgical margins and tumor grade prognostically influenced LRFS, MFS and OS.

FIGO IVB (para-aortic lymph adenopathy) squamous cell carcinoma of uterine cervix associated with a left pelvic kidney: a therapeutic challenge.

The standard of care for locally advanced carcinoma of uterine cervix is concurrent chemoradiation therapy followed by intracavitary brachytherapy, when there is para-aortic lymphadenopathy, radiation field needs to be extended to para-aortic region. In the latter case dose limiting organs are spinal cord, kidneys and small intestine. We present a challenging case of FIGO IVB squamous cell carcinoma of cervix and a pelvic kidney. This patient received chemoradiation to pelvis and para-aortic field, brachytherapy was not performed as patient already had undergone attempted hysterectomy. Treatment, outcome and challenges encountered in this case are presented and literature is reviewed.

Nasopharyngeal carcinoma - an update of treatment and acute radiation induced reactions from a tertiary-care hospital in Pakistan.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) is a diverse entity with a multi-factorial etiology and a distinct racial and geographical distribution. It is curable if diagnosed and treated early. METHODS: This descriptive study covered 30 patients who underwent radiotherapy (RT) for nasopharyngeal malignancies during February 2006 till November 2010 at the Department of Radiation Oncology, Aga Khan University Hospital (AKUH), Karachi. RESULTS: Thirty cases of nasopharyngeal tumors were registered; a case of embryonal rhabdomyosarcoma and another of diffuse large B-cell lymphoma were not included in the final analyses. There were 20 (71.0%) males and 8 (29.0%) females, 2 and 5 being observed in adolescents. The mean age of the male and female patients was 43.7 [SD 20.1] and 30.3 years [SD 17.9], respectively. Nodal involvement was seen in 23 cases and cranial in 8. Almost two-thirds the patients presented with a stage IV disease and all but two received chemotherapy. Electrons or photons were used for 23 cases; low anterior neck field was used in 25 cases. The doses of radiotherapy delivered ranged between 2000cGy to 7400cGy, the lower ones being given for palliation only. Once spinal cord tolerance was reached, electron boost fields were used in order to treat the posterior neck. A nasogastric tube was required for feeding in 2 (10.0%) male and 2 (25.0%) female patients; gastrostomy was needed for 1 (5.0%) patient. Radiotherapy (RT) induced reactions were observed in 90% of the patients, but were mild in most cases. CONCLUSIONS: In the presence of clinician based expertise and technical constraints in Pakistan, nasopharyngeal tumors are still being treated optimally with the need of creating a better awareness in public for early detection.

Extracranial meningioma: an unusual presentation of a mass over inner canthus of left eye.

Meningiomas are commonly encountered as intracranial brain tumours, but extracranial meningiomas do occur although seen rarely. Here we present a case of extracranial meningioma presenting as a mass over the medial canthus of left eye and the glabella with extension into the left ethmoid sinuses, without any neurological symptoms or signs. The patient underwent surgical excision, plastic surgical reconstruction and adjuvant radiotherapy after 3-dimensional conformal treatment planning.

Modification and implementation of NCCN guidelines on prostate cancer in the Middle East and North Africa region.

A prostate cancer committee was established to modify the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) on Prostate Cancer for adaptation and implementation in the Middle East and North Africa (MENA) region. The objective was to enhance the multidisciplinary approach to the treatment of prostate cancer. The committee, comprising regional experts in the fields of urologic, medical, and radiation oncology, reviewed the 2009 version of the NCCN Guidelines on Prostate Cancer and suggested modifications based on the unique needs of the regions determined through published evidence and local expertise. The committee identified several areas in the NCCN Guidelines that they believed required modification, which are presented in this article. The treatment of prostate cancer in the MENA region has numerous challenges. The hope is that this effort to modify the NCCN Guidelines on Prostate Cancer for practical use in the MENA region will improve regional awareness and patient care.

Lymphoma cases referred to the radiation oncology service of a tertiary referral university hospital in Karachi, Pakistan: a retrospective study.

INTRODUCTION: Radiation therapy is an important component of curative therapy for Lymphoma [Hodgkin's disease (HD) and non Hodgkin's Lymphoma (NHL)]. The current study was conducted to give us an overview of lymphoma patients presenting to a tertiary care hospital for complementary adjuvant RT. METHOD: Data of lymphoma patients who underwent radiotherapy during February 2006 till August 2009 at the department of radiation oncology, Aga Khan University, Hospital, Karachi was retrieved from the medical records and analyzed using SPSS (version 16.0). RESULTS: A total of 1,678 cancer patients were registered, 75 (0.45%) were lymphoma patients (25.3% HD; 74.7% NHL). HD and NHL were both seen predominantly in males, with a male:female ratio of 2 and 3 respectively. Nodal HD comprised 94.7% and nodal NHL comprised 41.1%. Extranodal NHL (EN-NHL) comprised 53.6% whereas 5.4% cases had both nodal and EN-NHL; 6.7% of EN-NHL were primary CNS lymphomas. Stages of presentation for HD were IIA (52.6%), 1A (21.1%), IIB (10.5%) and IB, IIIB and IVA collectively 15.9%. The ages of HD patients ranged from 11 to 54 years (median 23.5 years 13.2 SD). Response to therapy for HD was 52.6% complete remission, 36.8% partial response, and 5.3% each with stable and progressive disease. Almost all patients (94.7%) received radical treatment with radiation doses (between 1950 cG to 5404 cGy) with a median of 40 Grays.Stages at presentation for NHL were II (23.2%), IV (21.4%) and IE (17.9%); I, IIE, and III were found to be 12.5 %. NHL patients ranged from 15 to 88 years. It was more commonly observed amongst the elderly with 25% patients diagnosed in the fifth decade of life; 50% patients aged at or above 50 years, 41.1% belonged to the 25-49 years age group and 8.9% below 25 years of age. Majority of the cases were diffuse NHL (82.1%), follicular NHL (7.1%), Primary CNS unclassified type (8.9%), and unclassified other than CNS variety (1.8%). Response to chemotherapy for NHL was 51.8% complete remission, 25.9% progressive disease, 20.4% partial response. Forty (71.4%) patients with NHL received radical treatment with radiation doses between 2340 cG to 6600 cGy; 28.6% received palliative RT. CONCLUSION: Radiation therapy though important for curative lymphoma therapy, is relatively underutilized in our population, despite encouraging outcomes.

Ewing's sarcoma/PNET of kidney in 13-year-old girl.

Ewing's sarcoma is the second most common primary tumour of bone in childhood. Less frequently it occurs in soft tissues. Ewing's sarcoma/primitive neuroectodermal tumour (ES/PNET) is an extra ordinarily rare primary tumour in the kidney. Only very few cases of primary renal Ewing's sarcoma have been reported in the literature to date. We present a case of primary right renal Ewing's sarcoma in a 13-year-old girl who was diagnosed as a case of stage IV ES/PNET of kidney with metastases to lung and liver. Right nephrectomy was done followed by adjuvant radiotherapy and chemotherapy with complete response to local and distant area.