Venkatesh Rangarajan

NASOPHARYNGEAL CARCINOMA IN CHILDREN: COMPARISON OF CONVENTIONAL AND INTENSITY-MODULATED RADIOTHERAPY

PURPOSE To evaluate the efficacy of intensity-modulated radiotherapy (IMRT) in reducing the acute toxicities associated with conventional RT (CRT) in children with nasopharyngeal carcinoma. PATIENTS AND METHODS A total of 36 children with nonmetastatic nasopharyngeal carcinoma, treated at the Tata Memorial Hospital between June 2003 and December 2006, were included in this study. Of the 36 patients, 28 were boys and 8 were girls, with a median age of 14 years; 4 (11%) had Stage II and 10 (28%) Stage III disease at presentation. All patients had undifferentiated carcinoma and were treated with a combination of chemotherapy and RT. Of the 36 patients, 19 underwent IMRT and 17 underwent CRT. RESULTS After a median follow-up of 27 months, the 2-year locoregional control, disease-free, and overall survival rate was 76.5%, 60.6%, and 71.3%, respectively. A significant reduction in acute Grade 3 toxicities of the skin (p = 0.006), mucous membrane (p = 0.033), and pharynx (p = 0.035) was noted with the use of IMRT. The median time to the development of Grade 2 toxicity was delayed with IMRT (skin, 35 vs. 25 days, p = 0.016; mucous-membrane, 39 vs. 27 days, p = 0.002; and larynx, 50 vs. 28 days, p = 0.009). The duration of RT significantly influenced disease-free survival on multivariate analysis (RT duration >52 days, hazard ratio = 5.49, 95% confidence interval, 1.14-26.45, p = 0.034). The average mean dose to the first and second planning target volume was 71.8 Gy and 62.5 Gy with IMRT compared with 66.3 Gy (p = 0.001) and 64.4 Gy (p = 0.046) with CRT, respectively. CONCLUSION The results of our study have shown that IMRT significantly reduces and delays the onset of acute toxicity, resulting in improved tolerance and treatment compliance for children with nasopharyngeal carcinoma. Also, IMRT provided superior target coverage and normal tissue sparing compared with CRT.

Diagnostic performance of response assessment FDG-PET/CT in patients with head and neck squamous cell carcinoma treated with high-precision definitive (chemo)radiation.

PURPOSE To prospectively assess diagnostic performance of response assessment fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in patients with HNSCC treated with high-precision definitive (chemo)radiation. METHODS Fifty-seven patients treated on a prospective clinical trial having post-treatment response assessment FDG-PET/CT scans were included. Clinico-pathologic findings and follow-up information was considered as reference standard. RESULTS First response assessment FDG-PET/CT was done at a median of 9 weeks (inter-quartile range 8-10 weeks) from completion of treatment. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of first response assessment FDG-PET/CT for identifying residual disease at primary site was 50%, 91.8%, 50%, 91.8%, and 86%. The corresponding figures for the neck were 62.5%, 98%, 83.3%, 94.1%, and 93%. With a median follow-up of 26 months (range 7-45 months), the 3-year loco-regional control (83.9% vs 58.3%, p=0.001) and overall survival (68.8% vs 58.3%, p=0.063) was significantly better in patients with negative response assessment scans. CONCLUSION The overall diagnostic accuracy of response assessment FDG-PET/CT is good, but its sensitivity and PPV is somewhat low, particularly for primary site. A negative response assessment FDG-PET/CT scan is highly suggestive of absence of viable disease that could be used to guide decision-making.

Therapeutic Response to Radiofrequency Ablation of Neoplastic Lesions: FDG PET/CT Findings

Ablation of neoplastic lesions by using radiofrequency energy is gaining popularity in clinical practice because of the minimally invasive nature of radiofrequency ablation (RFA). Primary and secondary tumors of the liver and lung are treated with RFA when surgery is precluded because of comorbidity. Benign bone tumors are also treated with RFA to relieve pain and prevent further tumor growth. Differentiation between postablation tissue changes and residual disease is difficult with morphologic imaging modalities such as ultrasonography, computed tomography (CT), and magnetic resonance (MR) imaging, thus limiting the use of these modalities to detection of residual disease early after RFA. Fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) is a functional imaging modality that can be used to study the effects and efficacy of RFA. Lesions that show increased FDG uptake at PET become completely photopenic immediately after RFA, a finding that is suggestive of the completeness of ablation. Focal areas of increased FDG uptake within the ablated zone are suggestive of residual disease. Reactive tissue changes such as inflammation are depicted in the periphery of the ablated lesion and show a uniform low-grade FDG uptake, which can be differentiated from the focal, nodular intense uptake in areas of residual disease. Use of combined FDG PET/CT to detect residual disease early after RFA allows ablation to be repeated, if necessary, to obtain the maximum therapeutic benefit. Note that FDG uptake in the complications sometimes associated with RFA can be a cause of potential false-positive PET results.

Combined PET and Biopsy Evidence of Marrow Involvement Improves Prognostic Prediction in Diffuse Large B-Cell Lymphoma

Bone marrow is an important extranodal site in diffuse large B-cell lymphoma (DLBCL), and marrow histology has been incorporated into the new National Comprehensive Cancer Network international prognostic index. Marrow involvement demonstrated histologically confers poor prognosis but is identified by staging PET in more cases. How information from staging PET and biopsy should be combined to optimize outcome prediction remains unclear. Methods: The International Atomic Energy Agency sponsored a prospective international cohort study to better define the use of PET in DLBCL. As a planned subsidiary analysis, we examined the interplay of marrow involvement identified by PET and biopsy on clinical outcomes. Results: Eight countries contributed 327 cases with a median follow-up of 35 mo. The 2-y outcomes of cases with no evidence of marrow involvement (n = 231) were 81% (95% confidence interval [CI], 76%–86%) for event-free survival (EFS) and 88% (83%–91%) for overall survival (OS); cases identified only on PET (n = 61), 81% (69%–89%) for EFS and 88% (77%–94%) for OS; cases indentified only on biopsy (n = 10), 80% (41%–95%) for EFS and 100% for OS; or cases identified by both PET and biopsy (n = 25), 45% (25%–64%) for EFS and 55% (32%–73%) for OS. The hazard ratios for PET-negative/biopsy-negative cases versus PET-positive/biopsy-positive cases were 2.67 (95% CI, 1.48–4.79) for EFS and 3.94 (1.93–8.06) for OS. Conclusion: This large study demonstrates that positive iliac crest biopsy histology only confers poor prognosis for patients who also have abnormal marrow 18F-FDG uptake identified on the staging PET scan. Abnormal 18F-FDG uptake in marrow, when iliac crest biopsy histology is normal, has no adverse effect on outcomes.

Does PET–CT scan have a role prior to radical re-resection for incidental gallbladder cancer?

BACKGROUND Radical re-resection is offered to patients with non-metastatic, invasive, incidental gallbladder cancer. Data evaluating (18)F-fluorodeoxyglucose positron emission tomography-computed tomography ((18)F-FDG PET-CT) in patients with incidental gallbladder cancer is sparse. AIM To evaluate the efficacy of integrated (18)F-FDG PET-CT in determining occult metastatic or residual local-regional disease in patients with incidental gallbladder cancer. METHODS Patients referred with incidental gallbladder cancer for radical re-resection were evaluated using multidetector computed tomography (MDCT) and PET-CT. Based on preoperative imaging, 24 out of 92 patients were found suitable for surgery. The two imaging modalities were evaluated with respect to residual and resectable disease. RESULTS In determining residual disease, MDCT had a sensitivity and positive predictive value (PPV) of 42.8%, each, while PET-CT had a sensitivity and PPV of 28.5 and 20%, respectively. In determining resectability, MDCT had a sensitivity, PPV, and accuracy of 100, 87.5, and 87.5%, respectively, as compared to PET-CT (sensitivity=100%, PPV=91.3%, accuracy=91.6%). CONCLUSIONS From our study, it appears that in patients with incidental gall bladder cancer without metastatic disease, PET-CT and MDCT seem to have roles complementing each other. PET-CT was able to detect occult metastatic or residual local-regional disease in some of these patients, and seems to be useful in the preoperative diagnostic algorithm of patients whose MDCT is normal or indicates locally advanced disease.

Integrated PET/CT in evaluating sarcomatous transformation in osteochondromas.

Aim: To study the role of PET-CT in evaluating sarcomatous transformation in osteochondromas. Materials and Methods: This was a retrospective analysis of a prospective data base of 12 patients from 2005 to 2007 with a clinical diagnosis of an osteocartilaginous lesion who were referred for a FDG PET-CT study to evaluate for possible malignant transformation. Imaging was performed on a GE Discovery ST PET-CT system after intravenous injection of 370 MBq (10 mCi) of F-18 FDG. Results: Seven patients with histopathological evidence of a sarcomatous transformation to grade II chondrosarcoma showed moderate to high FDG uptake (SUV 3.3–6.9), whereas 1 patient with a dedifferentiated chondrosarcoma showed a focus of very intense uptake (SUV 11.4). Four patients with histopathological and/or clinical or follow-up diagnosis of a benign osteocartilaginous lesion showed low grade FDG uptake (SUV 0.8–1.3). FDG uptake was also noted in an asymptomatic osteochondroma which on histopathology revealed a grade II chondrosarcoma. Conclusions: Whole body FDG PET-CT is an important adjunct to conventional morphologic imaging in evaluating suspected malignant transformation in osteochondromas. Increased glucose metabolism can help diagnose sarcomatous transformation at the suspected sites as well as detect early malignant change at clinically unsuspected sites. Moreover, its ability to detect a focus of dedifferentiation can be useful for prognostication and to plan adjuvant treatment. A small cohort limits statistically sound conclusions to be drawn from this study, however further prospective trials based on these findings can help explore the potential application of FDG PET-CT in this clinical condition.

Functional imaging in primary tumour-induced osteomalacia: relative performance of FDG PET/CT vs somatostatin receptor-based functional scans: a series of nine patients.

Localization of phosphatonin‐producing mesenchymal tumours in patients with primary tumour‐induced osteomalacia (pTIO) is challenging. Functional imaging plays an important role in the localization of these tumours.

Prospective randomized controlled trial to compare 3‐dimensional conformal radiotherapy to intensity‐modulated radiotherapy in head and neck squamous cell carcinoma: Long‐term results

Grade ≥2 acute xerostomia between 3D conformal radiotherapy (RT) and intensity‐modulated radiotherapy (IMRT) was evaluated in patients with head and neck squamous cell carcinomas (HNSCCs) treated radically.

18F-FDG PET/CT-directed biopsy: does it offer incremental benefit?

PurposeTo study whether the metabolic information provided by a prior PET/computed tomography (CT) scan can add valuable information and an incremental benefit while performing image-guided biopsies. MethodsFluorine-18 fluorodeoxyglucose (18F-FDG) PET/CT findings of 112 patients were available before biopsy and were considered for analysis. Biopsies were performed using standard techniques only after the needle tip was confirmed to be in the portion of the lesion corresponding to the hypermetabolic area seen on PET. This was achieved by visual coregistration and also by software registration algorithms that registered the intraprocedural CT images with the preselected PET/CT data. Only those biopsies for which a definitive histopathological diagnosis could be made were considered ‘diagnostic’. Cases in which PET/CT added an incremental value were divided into three categories. ResultsA total of 112 patients (66 male and 46 female, age range 16–74 years) underwent a biopsy based on PET findings. The biopsy sites were as follows: lung, 54; lymph nodes, 27; bone, 12; and soft-tissue masses/deposits, 19. Out of the 112 biopsies, an incremental benefit was seen overall in 53 patients (47.3%): in 40.7% (22/54) of patients who underwent lung biopsies, 44.4% (12/27) of those who underwent lymph node biopsies, 66.6% (8/12) of those who underwent bone biopsies and 57.8% (11/19) of those who underwent soft-tissue biopsies. Out of the cases that showed an incremental benefit, the highest number (30) belonged to the category in which the biopsy sample was obtained from the focal hypermetabolic portion of the apparently larger morphological lesion seen on CT. ConclusionPET/CT data coregistered with intraprocedural CT images can guide needle placement in the viable portion of the lesion, thus increasing the chances of achieving a definitive diagnosis. This approach can offer a significant incremental benefit while performing image-guided biopsies.

Etiology and significance of incidentally detected focal colonic uptake on FDG PET/CT.

Background: Incidental colonic uptake of 18F-flurodeoxyglucose (FDG) is not an infrequent finding encountered during whole body positron emission tomography (PET) imaging. Almost all studies on this topic are in Western populations, which have a markedly different epidemiological profile for colorectal premalignant and malignant conditions as compared to that of the Indian subcontinent. Aim: The purpose of this study was to assess the etiology of incidentally detected focal FDG uptake in the colon by comparing it with colonoscopy and histopathology. Materials and Methods: Electronic medical records of patients who underwent FDG PET/computed tomography (CT) at our institution for a 2½-year period from January 2009 to July 2011 were reviewed. There were 32 out of 9000 (0.35%) patients whose PET/CT reports mentioned incidental focal colonic FDG uptake, of which 24 patients subsequently underwent colonoscopy. Lesions which appeared neoplastic on colonoscopy were confirmed with histopathology obtained after biopsy or surgery. Colonoscopy and pathology findings were considered as gold standard. Results: Among the 24 patients who underwent a colonoscopy, 3 patients had normal findings (12.5%). A positive colonoscopy was noted in 21 patients (87.5%) with the lesion coinciding with the location described in the PET/CT report. Adenomatous polyps were detected in 12 patients (37.5%), whereas in 8 patients (25%) malignant lesions were confirmed [adenocarcinoma n = 5, non-Hodgkins lymphoma (NHL) n = 2, malignant melanoma n = 1]. In one patient, colonic uptake was diagnosed as inflammatory. The mean standardized uptake valuemax (SUVmax) for the 12 premalignant lesions was 16.9 ± 9.6 (range 7.5-37.4) and the mean SUVmax for the 8 malignant lesions was 12.9 ± 5.5 (range 6.7-21.6). The difference in SUVmax between the premalignant adenomatous polyps and the malignant lesions was not statistically significant (P = 0.316). Conclusions: Our study shows that a significant proportion of patients (62.5%, 20/32) showing an incidental focal FDG uptake will harbor premalignant (adenomatous polyps) or malignant lesions, and further evaluation with colonoscopy and biopsy is warranted in such cases.