Interim18 F-FLUORO-2-deoxy-d-glucose positron emission tomography scan/computed tomography scan in diffuse large B cell lymphoma-as a prognostic tool.

OBJECTIVE: To assess the role of interim [18F]-Fluoro-2-deoxy-d-glucose positron emission tomography scan/computed tomography scan in the management of diffuse large B-cell lymphoma in terms of progression-free survival and overall survival prediction. METHODS: The retrospective study was conducted at the Shaukat Khanum Memorial Cancer Hospital, Lahore, and comprised data of newly diagnosed patients of diffuse large B-cell lymphoma treated between January 2010 and June 2013.Baseline characteristics of patients were documented and compared. Response on interim positron emission tomography/computed tomography and end of treatment scan was taken a look at, and .progression-free survival and overall survival for positive/negative scans were calculated. Data was also reviewed for sensitivity, specificity, positive predictive value and negative predictive value for relapse. SPSS 19 was used for statistical analysis. RESULTS: Data of 119 patients was reviewed, and 87(73%) of them were males. Overall median age was 33 years (range 18-50). Interim scan was positive for 63(53%) patients and negative for 53(47%), and showed positive predictive value, negative predictive value, sensitivity and specificity for relapse of 35%, 89%, 79% and 55% respectively. Two-years progression-free survival and overall survival for scan-positive patients was 66% and 72% compared to 88% (p=0.002) and 92% (p=0.005) for scan-negative patients. Corresponding values at 2 years for patients having positive end-of-treatment scan were 35% and 44% against 94% (p< 0.001) and 96%(p< 0.001) for patients with negative scan. CONCLUSIONS: Interim positron emission tomography/computed tomography had high sensitivity and negative predictive value for relapse in diffuse large B-cell lymphoma. Both interim and end-of-treatment scans were predictors of progression-free survival and overall survival.

Secondary malignant melanoma in primary mediastinal germ cell tumour.

Secondary transformation in Germ Cell Tumours (GCT) is an extremely rare event. We report here a case of malignant melanoma arising in primary mediastinal GCT. A young male presented with new onset dyspnoea and a mediastinal mass. As serum alpha fetoprotein was raised, a diagnosis of primary mediastinal GCT was made. He achieved remission with standard chemotherapy and resection of the mass. After a year, he relapsed with widespread disease which on work-up revealed malignant melanoma. As examination for cutaneous melanoma was unremarkable, a diagnosis of mediastinal GCT with secondary transformation to melanoma was made. Exact origin of melanoma in GCTs is unknown, but these may occur from transformation of dermal elements or de-differentiation of germ cells to melanomas. Before making such a diagnosis, search for primary cutaneous melanoma is mandatory. No clear guidelines exist in literature for the treatment of secondary melanomas, so current management guidelines for cutaneous melanoma may be followed.

Impact of rituximab and IPI on survival in diffuse large B cell lymphoma patients treated at a tertiary level cancer centre in Pakistan: a single-centre experience.

OBJECTIVE: To determine the impact of Rituximab and international prognostic index score on survival in diffuse large B-cell lymphoma patients. METHOD: The retrospective study was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, from January to May 2013 and comprised record of patients with diffuse large B-cell lymphoma who were treated from 2007 to 2010. Baseline international prognostic index score, stage at presentation were noted and the records were divided into two groups A and B on the basis of the type of chemotherapy. SPSS 19 was used for statistical analysis. RESULTS: Of the 93 patients in the study whose records were reviewed, 54(58%) were men. Overall median age was 43 years (range: 18-76). Stages at presentation were stage-I 14 (15.1%), stage-II 41 (44.1%), stage-III 20 (21.5%) and stage-lV 18 (19.4%). International prognostic index risk categorisation was low risk 59 (63.4%), low intermediate risk 23 (24.7%), high intermediate risk 10 (10.8%) and high risk 1 (1.1%). There were 31 (33%) patients in Group A and 62 (67%) in Group B. Median follow-up was 3.9 years (range: 1.2-6.1). Overall survival at 4 years was 66.4%; for Group A 65.3% and for Group B 66.7% (p < 0.4). On the basis of risk categories, overall survival was statistically significant (p < 0.001) between the groups. CONCLUSION: International prognostic index risk categorisation had statistically significant impact on survival. However, there was no evidence of a significant survival benefit between types of chemotherapy. Further controlled trials are needed in this regard.

Safe negative margin width in breast conservative therapy: results from a population with a high percentage of negative prognostic factors.

BACKGROUND: There remains a controversy in the literature regarding adequate width of negative surgical margins in breast conservative therapy (BCT). It is now advocated that no tumor on an inked margin is a safe negative margin. Majority of studies on the outcomes of BCT had patients with favorable prognostic factors. Pakistani population has a high expression of unfavorable prognostic factors. The objective of this study was to determine a safe negative margin width in Pakistani population that undergoes BCT. METHODS: A total of 603 patients with identifiable surgical margins underwent BCT from 1997 to 2009 in Shaukat Khanum Cancer Hospital. Patients were divided into close (≤2 mm), free (>2-10 mm), and wide (>10 mm) margin groups. Locoregional recurrence was defined as recurrence within the operated breast, ipsilateral axilla, or supraclavicular or internal mammary lymph nodes. Locoregional recurrence-free survival was calculated from the date of surgery to the date of locoregional recurrence. Five-year locoregional recurrence-free survival was determined for margin groups. Univariate and multivariate Cox proportional hazard analyses were performed to determine independent predictors of locoregional recurrence. RESULTS: A total of 415 (69 %) patients were <50 years of age. There were 82 (15 %) T3/T4, 337 (56 %) poorly differentiated, and 238 (39 %) ER/PR -ve tumors. Nodal positivity was present in 314 (52 %) patients. The actual number of locoregional recurrences was 16 (12 %), 8 (3 %), and 10 (4.6 %), respectively (P = 0.002). Expected 5-year locoregional recurrence-free survival was 90, 97, and 96 %, respectively (P = 0.002). On multivariate analysis, tumor size, nodal involvement, and negative margin width were independent predictors of locoregional recurrence. CONCLUSION: A negative margin width of 2 mm might represent an adequate negative margin width in the Pakistani population undergoing breast conservative therapy.

Malignant transformations in ovarian teratomas: a report of four cases.

Mature cystic teratoma (MCT) is a common ovarian neoplasm in young females. A secondary malignant transformation occurs rarely in cystic teratomas at an older age. These secondary malignant neoplasms most commonly are squamous cell carcinomas (SCCs). Various mechanisms are reported, but the exact aetiology is unknown. We report three cases of SCC arising in cystic teratoma and one case of papillary thyroid neoplasm as secondary transformation. The SCCs were arising from the cyst wall, while the papillary thyroid malignancy arose from the normal-looking thyroid epithelium. Histologically, all SCC cases were poorly differentiated. Poor prognostic features for secondary transformations include size more than 10 cm, older age and rapid growth. Data is scarce regarding their appropriate treatment. However, surgical debulking is necessary. Platinum-based adjuvant regimens and taxanes are recommended in cases of advanced disease. In this paper we review and share our experience with this rare disorder.

Factors affecting outcome of patients with multiple myeloma.

BACKGROUND: Multiple myeloma is a heterogeneous disease, with wide survival range and multiple risk factors and staging systems linked to survival. The objective of this study was to assess the overall survival of patients with multiple myeloma (MM) diagnosed and treated at Shaukat Khanum Memorial Cancer Hospital (SKMCH), Lahore with respect to various prognostic factors. METHODS: This was a survival analysis with data collected retrospectively on 82 patients fulfilling the diagnostic criteria of multiple myeloma. Overall survival was studied in relation to International Staging System (ISS), renal failure (Serum creatinine >2 mg/dl), anaemia (Hemoglobin <10 mg/dl), bone involvement (presence of lytic lesion on skeletal survey) and hypercalcemia (serum calcium >11mg/dl) due to multiple myeloma at the time of diagnosis. RESULTS: Mean age of patients was 61 years, including 67% males and 33% females. Median overall survival for ISS stage-I (24%), stage-II (44%) and stage-III (32%) was 58, 41 and 12 months respectively (p=0.01). Patients with renal impairment (16% of total) had median overall survival of 13 months compared to 41 months in patients without renal involvement (p=0.02). Hypercalcemia was noted in 27% patients with median overall survival of 32 months versus 38 months in patients without hypercalcemia, but its impact on survival was statistically insignificant (p=0.79). Similarly no significant impact on survival was noted in patients with bone involvement or anaemia found in 74 % and 38% of patient's respectively. CONCLUSIONS: ISS stage and renal failure due to multiple myeloma at presentation have a significant impact on survival. However, other prognostic factors like bone involvement, anaemia and hypercalcemia were not shown to influence survival significantly.

FDG-PET scan in assessing lymphomas and the application of Deauville Criteria.

OBJECTIVE: To evaluate the role of Fluorine-18-fluorodexoyglucose Positron Emission Tomography (FDG-PET) scan in staging and its implications on the treatment of lymphoma, and to study the concordance between visual assessment and Deauville criteria for the interpretation of interim scans. METHODS: The prospective single-arm experimental study was conducted at the Shaukat Khanum Memorial Cancer Hospital, Lahore, from May 2011 to October 2011. It comprised 53 newly diagnosed lymphoma patients who agreed to participate in the study. All patients underwent scans with contrast-enhanced computerised tomography at baseline. Treatment plan was formulated based on the final stage. Interim scans were acquired after 2 cycles of chemotherapy and were reported using visual criteria and compared with the 5-point Deauville criteria. Score of 1-3 was taken as disease-negative, while 4-5 was taken as disease-positive. SPSS 19 was used for statistical analysis. RESULTS: Of the 53 patients, 35 (66%) had Hodgkin's Lymphoma, while 18 (34%) had Non-Hodgkin's Lymphoma. Scans resulted in disease upstaging in 4 (7.5%) patients, and detecting increased disease burden in 12 (23%). On interim scans, complete remission was achieved in 38 (71%) patients (Deauville score 1-3); 12(23%) showed partial response (Deauville score 4-5); and 3 (6%) had progression. Kappa test was statistically significant (kappa 0.856; p <0.001). CONCLUSION: The positron emission tomography helped to upstage lymphoma and reflected increased disease burden. The Deauville criteria correlated very well with visual assessment criteria and can be applied in the patient population.

Ifosfamide neurotoxicty in a young female with a remarkable response to thiamine.

Ifosfamide, a commonly used chemotherapeutic agent in various regimens for many malignancies and has a well known central nervous system side effect. Ifosfamide induced encephalopathy develops in approximately 10-30% of patients exposed to the drug. It is generally reversible after discontinuing the therapy; however cases of fatal neurotoxicity have been reported in literature. Commonly used antidote, Methylene blue; has a moderate efficacy in reversing the encephalopathy followed by lesser response rates by Thiamine. We submit a case report of a young female patient with refractory diffuse large B cell lymphoma who developed severe ifosfamide neurotoxicity. With the use of intravenous thiamine, encephalopathy resolved in our patient within a mean time of 30 hours (average range is 10-30 hours). We found Thiamine to be safe and effective in treatment for ifosfamide induced encephalopathy.

Experience with neoadjuvant chemotherapy in patients with breast cancer.

OBJECTIVE: To determine the response rates to neoadjuvant chemotherapy in patients with breast cancer. METHODS: Medical records of 161 women with breast cancer, registered at Shaukat Khanum Memorial Cancer Hospital between July 2006 and March 2008 were retrospectively reviewed. Patients were stratified into two groups based on the type of chemotherapy received; Group A (Anthracycline based regimens), Group B (Anthracycline and Taxane based regimens). Response rate was noted. RESULTS: Clinical complete response rates by clinical examination were significantly higher in Group B as compared to Group A in both primary disease in breast and axillary nodes (39% vs. 20.3%, p = 0.01; 72.7% vs. 30.7%, p = 0.01, respectively). There was no difference in response rates by imaging between groups A and B in breast and axillary lymph nodes (12.5% vs. 17%, p = 0.4; 66.6% vs. 70.4%, p = 0.4, respectively). There was no difference in pCR rates between Group A and B (9.1% vs. 14.2%, p = 0.35). However, multivariate analysis showed significant increase in pCR rates by addition of taxanes (p = 0.028), in patients with poorly differentiated tumours (p = 0.028) and in those with axillary node negative disease by palpation (p = 0.016). There was no statistically significant difference in breast conservation rates between group A and B (25.4% vs. 36.7%, p = 0.1). CONCLUSION: Addition of taxanes to anthracycline based regimens improved the pathological complete response in our patients with breast cancer.

Adrenal myelolipoma: a report of three cases and review of literature.

Adrenal myelolipoma is a rare and benign tumour composed of mature adipose tissue and haematopoietic elements that resemble bone marrow. It is mostly discovered incidentally on imaging of abdomen done for non adrenal related reasons or at autopsy. Usually asymptomatic, but has been reported to present with symptoms such as flank pain resulting from tumour bulk, necrosis or spontaneous retroperitoneal haemorrhage. Symptomatic tumours, growing tumours or tumours larger than 10 cm should be excised surgically. We report cases of 3 male patients presenting with flank pain and upper pole renal masses. All three were treated surgically with adrenalectomy. Myelolipoma was confirmed in all three on histology.