Topical 5-Fluorouracil 1% as Primary Treatment for Ocular Surface Squamous Neoplasia.

PURPOSE: To determine the efficacy of topical 5-fluorouracil 1% (5-FU) as a primary treatment of ocular surface squamous neoplasia (OSSN). DESIGN: Retrospective study. PARTICIPANTS: Topical 5-FU was used as primary therapy in 44 patients with OSSN. METHODS: 5-Fluorouracil 1% administered topically 4 times daily for 1 week followed by a drug holiday of 3 weeks. Patients were identified through a pharmacy database. Patients were excluded if 5-FU was used as adjuvant therapy, if they did not complete therapy, or if they were still actively receiving treatment for OSSN at the time of last follow-up. MAIN OUTCOME MEASURES: The primary outcome measures were the frequency of complete resolution with topical 5-FU treatment and the rate of OSSN recurrence. RESULTS: Of the 44 patients identified, 32 were men and 12 were women. The mean age was 68 years. Complete resolution of OSSN was noted in 82% of patients (36/44); 18% (8/44) were considered treatment nonresponders. Patients were treated with a median of 4 cycles (range, 2-9 cycles). Nasal location was the only risk factor identified for nonresponse to therapy (P = 0.04). The median follow-up after resolution was 10 months (range, 2-77 months). In the 36 patients who showed complete resolution, 4 experienced tumor recurrence. Recurrence rates at 1 and 2 years were 6% and 15%, respectively, using Kaplan-Meier survival analysis. At least 1 side effect from the medication was reported by 61% of patients (21/44), but only 1 patient discontinued the medication because of intolerance. The most common side effect was pain (n = 17; 39%), followed by tearing (n = 10; 23%), photophobia (n = 6; 14%), itching (n = 4; 9%), swelling (n = 2; 5%), and infection (n = 1; 2%). No long-term complications were reported. CONCLUSIONS: 5-Fluorouracil is effective and well tolerated as a primary treatment for OSSN, with 82% of tumors responding completely to therapy.

Marsupialized fungal mycetoma masquerading as conjunctival melanoma.

PURPOSE: To report a case of a fungal mass misdiagnosed as a pigmented conjunctival melanoma. METHOD: Case report. RESULT: A 38-year-old woman was referred for a pigmented conjunctival lesion that was diagnosed as a melanoma. She had a history of a scleral buckle in that eye for retinal detachment 2 years before presentation. Slit-lamp examination revealed a pigmented mass from the 11- to 2-o'clock position. This was noted to be imbricated within the invagination of a conjunctival fold from the previous surgery. The mass was removed, cultured, and confirmed to be a fungal infection from Scytalidium sp. CONCLUSIONS: Scleral buckles can cause folds in the conjunctiva, which can be foci for fungal infection.

Management of conjunctival malignant melanoma: a review and update.

Conjunctival malignant melanoma is a pigmented lesion of the ocular surface. It is an uncommon but potentially devastating tumor that may invade the local tissues of the eye, spread systemically through lymphatic drainage and hematogenous spread, and recur in spite of treatment. Despite its severity, the rarity of available cases has limited the evidence for diagnosis and management. This review will provide an overview of the epidemiology, presentation, diagnosis, management, and surveillance of conjunctival melanoma, with an emphasis on recent advances in biological therapies to treat this disease.

Interfractional variations in the setup of pelvic bony anatomy and soft tissue, and their implications on the delivery of proton therapy for localized prostate cancer.

PURPOSE: To quantify daily variations in the anatomy of patients undergoing radiation therapy for prostate carcinoma, to estimate their effect on dose distribution, and to evaluate the effectiveness of current standard planning and setup approaches employed in proton therapy. METHODS: We used series of computed tomography data, which included the pretreatment scan, and between 21 and 43 in-room scans acquired on different treatment days, from 10 patients treated with intensity-modulated radiation therapy at Morristown Memorial Hospital. Variations in femur rotation angles, thickness of subcutaneous adipose tissue, and physical depth to the distal surface of the prostate for lateral beam arrangement were recorded. Proton dose distributions were planned with the standard approach. Daily variations in the location of the prescription isodose were evaluated. RESULTS: In all 10 datasets, substantial variation was observed in the lateral tissue thickness (standard deviation of 1.7-3.6 mm for individual patients, variations of >5 mm from the planning computed tomography observed in all series), and femur rotation angle (standard deviation between 1.3° and 4.8°, with the maximum excursion exceeding 10° in 6 of 10 datasets). Shifts in the position of treated volume (98% isodose) were correlated with the variations in the lateral tissue thickness. CONCLUSIONS: Analysis suggests that, combined with image-guided setup verification, the range compensator expansion technique prevents loss of dose to target from femur rotation and soft-tissue deformation, in the majority of cases. Anatomic changes coupled with the uncertainties of particle penetration in tissue restrict possibilities for margin reduction in proton therapy of prostate cancer.

Potential for higher treatment failure in obese patients: correlation of elevated body mass index and increased daily prostate deviations from the radiation beam isocenters in an analysis of 1,465 computed tomographic images.

PURPOSE: Recent clinical outcome studies on prostate cancer have reported the influence of patient's obesity on the biochemical failure rates after various treatment modalities. In this study, we investigated the effect of patient's physical characteristics on prostate shift in external beam radiotherapy (EBRT) and hypothesized that there maybe a correlation between patient physique and tumor shift. METHODS AND MATERIALS: A retrospective analysis was performed using data for 117 patients who received image-guided radiation therapy (IGRT) for prostate cancer between January 2005 and April 2007. A total of 1,465 CT scans were analyzed. The standard deviations (SDs) of prostate shifts for all patients, along with patient weight, body mass index (BMI), and subcutaneous adipose-tissue thickness (SAT), were determined. Spearman rank correlation analysis was performed. RESULTS: Of the 117 patients, 26.5% were considered normal weight, 48.7% were overweight, 17.9% were mildly obese, and 6.9% were moderately to severely obese. Notably 1.3%, 1.5%, 2.0%, and 21.2% of the respective shifts were greater than 10 mm in the left-right (LR) direction for the four patient groups, whereas in the anterior-posterior direction the shifts are 18.2%, 12.6%, 6.7%, and 21.0%, respectively. Strong correlations were observed between SAT, BMI, patient weight, and SDs of daily shifts in the LR direction (p < 0.01). CONCLUSIONS: The strong correlation between obesity and shift indicates that without image-guided radiation therapy, the target volume (prostate with or without seminal vesicles) may not receive the intended dose for patients who are moderate to severely obese. This may explain the higher recurrence rate with conventional external beam radiation therapy.

Interfractional prostate shifts: review of 1870 computed tomography (CT) scans obtained during image-guided radiotherapy using CT-on-rails for the treatment of prostate cancer.

PURPOSE: To review 1870 CT scans of interfractional prostate shift obtained during image-guided radiotherapy. METHODS AND MATERIALS: A total of 1870 pretreatment CT scans were acquired with CT-on-rails, and the corresponding shift data for 329 patients with prostate cancer were analyzed. RESULTS: Of the 1870 scans reviewed, 44% required no setup adjustments in the anterior-posterior (AP) direction, 14% had shifts of 3-5 mm, 29% had shifts of 6-10 mm, and 13% had shifts of >10 mm. In the superior-inferior direction, 81% had no adjustments, 2% had shifts of 3-5 mm, 15% had shifts of 6-10 mm, and 2% had shifts of >10 mm. In the left-right direction, 65% had no adjustment, 13% had shifts of 3-5 mm, 17% had shifts of 6-10 mm, and 5% had shifts of >10 mm. Further analysis of the first 66 consecutive patients divided into three groups according to body mass index indicates that the shift in the AP direction for the overweight subgroup was statistically larger than those for the control and obese subgroups (p < 0.05). The interfractional shift in the lateral direction for the obese group (1 SD, 5.5 mm) was significantly larger than those for the overweight and control groups (4.1 and 2.9 mm, respectively) (p < 0.001). CONCLUSIONS: These data demonstrate that there is a significantly greater shift in the AP direction than in the lateral and superior-inferior directions for the entire patient group. Overweight and obese patient groups show a significant difference from the control group in terms of prostate shift.

Image-guided radiotherapy for prostate cancer by CT-linear accelerator combination: prostate movements and dosimetric considerations.

PURPOSE: Multiple studies have indicated that the prostate is not stationary and can move as much as 2 cm. Such prostate movements are problematic for intensity-modulated radiotherapy, with its associated tight margins and dose escalation. Because of these intrinsic daily uncertainties, a relative generous "margin" is necessary to avoid marginal misses. Using the CT-linear accelerator combination in the treatment suite (Primatom, Siemens), we found that the daily intrinsic prostate movements can be easily corrected before each radiotherapy session. Dosimetric calculations were performed to evaluate the amount of discrepancy of dose to the target if no correction was done for prostate movement. METHODS AND MATERIALS: The Primatom consists of a Siemens Somatom CT scanner and a Siemens Primus linear accelerator installed in the same treatment suite and sharing a common table/couch. The patient is scanned by the CT scanner, which is movable on a pair of horizontal rails. During scanning, the couch does not move. The exact location of the prostate, seminal vesicles, and rectum are identified and localized. These positions are then compared with the planned positions. The daily movement of the prostate and rectum were corrected for and a new isocenter derived. The patient was treated immediately using the new isocenter. RESULTS: Of the 108 patients with primary prostate cancer studied, 540 consecutive daily CT scans were performed during the last part of the cone down treatment. Of the 540 scans, 46% required no isocenter adjustments for the AP-PA direction, 54% required a shift of > or =3 mm, 44% required a shift of >5 mm, and 15% required a shift of >10 mm. In the superoinferior direction, 27% required a shift of >3 mm, 25% required a shift of >5 mm, and 4% required a shift of >10 mm. In the right-left direction, 34% required a shift of >3 mm, 24% required a shift of >5 mm, and 5% required a shift of >10 mm. Dosimetric calculations for a typical case of prostate cancer using intensity-modulated radiotherapy with 5-mm margin coverage from the clinical target volume (prostate gland) was performed. With a posterior shift of 10 mm for the prostate, the dose coverage dropped from 95-107% to 71-100% coverage. CONCLUSION: We have described a technique that corrects for the daily prostate motion, allowing for extremely precise prostate cancer treatment. This technique has significant implications for dose escalation and for decreasing rectal complications in the treatment of prostate cancer.

A comparison of two image fusion techniques in ct-on-rails localization of radiation delivery.

A computed tomography (ct) scanner on Rails has been installed in a linear accelerator room at Morristown Memorial Hospital since 2000. The ct-on-Rails has been used for the localization of patient position during radiation delivery for prostate, lung and liver cancer patients. The image management system, the Siemens Syngo system, is the primary software employed in the registration of the planning ct and the treatment ct images. This study compares the two image fusion methods available in the system: Landmark Registration and Visual Alignment. Shifts in 6 ct scans with Rando phantom were deduced from Landmark Registration (automatic algorithm) and from Visual Alignment (manual registration), and compared with the shifts directly measured on the phantom. For Visual Alignment, the isocenter shifts deduced from the fused images generally agreed well with the directly measured shifts on the Rando phantom, with average absolute error of 0.9 mm in anterior-posterior (ap) direction, 1.0 mm in right-left (rl) direction, and 2.0 mm in superior-inferior (si) direction. The image fusion algorithm was confirmed to be accurate. Some scans with Landmark Registration gave erroneous ap shifts when the anterior radio-opaque marker (bb) registration was of in the ap direction. Visual Alignment was more robust than Landmark Registration in these clinical situations.

Are multiple markers the future of prostate cancer diagnostics?

Prostate specific antigen (PSA) is the most successful and widely employed cancer serum marker in use today. There is growing evidence that the introduction of wide PSA screening and earlier detection can result in decreased cancer mortality associated with a decline in metastatic disease. PSA circulates in a number of distinct forms. Measurement of these in addition to total PSA significantly increases diagnostic utility. Diagnostic utility is likely to be further increased by adding kallikreins, cytokines, growth factors, receptors and cellular adhesion factors to the biomarker panel. The need for multiple markers reflects the multidimensional nature of prostate disease which ranges from metastatic cancer to indolent cancer to benign hyperplasia and inflammation, all of which require distinct treatments and medical interventions.

Computed tomography localization of radiation treatment delivery versus conventional localization with bony landmarks.

A computed tomography (CT) scanner was installed in the linear accelerator room (Primatom) at Morristown. Since June 2000, we have been providing prostate, lung, and liver cancer patients with fusion of CT and linac radiation treatment. This paper describes our registration methods between planning and treatment CT images, and compares treatment localization by CT versus conventional localization by bony landmarks such as portal imaging. For image registration, we printed out beforehand the beam's eye view of the treatment fields. Prostate tumor volume from each Primatom CT slice was mapped on the printouts, and the necessary isocenter shift relative to the skin marks was deduced. No port film was necessary for our Primatom patients. For ten patients we generated digitally-reconstructed radiographs (DRRs) with bone contrast from the CT scans, and deduced the required shift as the difference between the DRRs of the Primatom CT versus the planning CT. This represented the best observable shift should portal imaging be employed. Shift from bony landmark significantly correlated with the Primatom CT shift. Positioning adjustment based on bony anatomy was generally in the same direction as the CT shift for individual patient, but frequently did not go far enough. Our study confirmed that prostate organ motion relative to the bones has an average length of 4.7 mm (with standard deviation of 2.7 mm), and indicated the superiority of CT versus conventional bony structure (such as portal imaging) localization.