Arnold C. Paulino

The role of fluorodeoxyglucose positron emission tomography in cervical lymph node metastases from an unknown primary tumor

The authors performed a comprehensive review of the efficacy of fluorodeoxyglucose positron emission tomography (FDG‐PET) in the detection of primary tumors in patients with cervical metastases from unknown primary tumors.

Pixel analysis of MR perfusion imaging in predicting radiation therapy outcome in cervical cancer

The purpose of this study was to assess heterogeneity of tumor microcirculation determined by dynamic contrast‐enhanced magnetic resonance (MR) imaging and its prognostic value for tumor radiosensitivity and long‐term tumor control using pixel‐by‐pixel analysis of the dynamic contrast enhancement. Sixteen patients with advanced cervical cancer were examined with dynamic contrast‐enhanced MR imaging at the time of radiation therapy. Pixel‐by‐pixel statistical analysis of the ratio of post‐ to precontrast relative signal intensity (RSI) values in the tumor region was performed to generate pixel RSI distributions of dynamic enhancement patterns. Histogram parameters were correlated with subsequent tumor control based on long‐term cancer follow‐up (median follow‐up 4.6 years; range 3.8–5.2 years). The RSI distribution histograms showed a wide spectrum of heterogeneity in the dynamic enhancement pattern within the tumor. The quantity of low‐enhancement regions (10th percentile RSI < 2.5) significantly predicted subsequent tumor recurrence (88% vs. 0%, P = 0.0004). Discriminant analysis based on both 10th percentile RSI and pixel number (reflective of tumor size) further improved the prediction rate (100% correct prediction of subsequent tumor control vs. recurrence). These preliminary results suggest that quantification of the extent of poor vascularity regions within the tumor may be useful in predicting long‐term tumor control and treatment outcome in cervical cancer. J. Magn. Reson. Imaging 2000;12:1027–1033.

CURATIVE RADIOTHERAPY FOR PRIMARY ORBITAL LYMPHOMA

PURPOSE To review our institutional experience with primary orbital lymphoma and determine the prognostic factors for survival, local control, and distant metastases. In addition, we also analyzed the risk factors for complications in the radiotherapeutic management of this tumor. METHODS AND MATERIALS Between 1973 and 1998, 47 patients (29 women [62%] and 18 men [38%], median age 69 years, range 32-89) with Stage IAE orbital lymphoma were treated with curative intent at one department. Five had bilateral orbital involvement. The tumor was located in the eyelid and extraocular muscles in 23 (44%), conjunctiva in 17 (33%), and lacrimal apparatus in 12 (23%). The histologic features according to the World Heath Organization classification of lymphoid neoplasms was follicular lymphoma in 25, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type in 8, diffuse large B-cell lymphoma in 12, mantle cell lymphoma in 6, and peripheral T-cell lymphoma in 1. For the purposes of comparison with the existing literature on orbital lymphomas, the grading system according to the Working Formulation was also recorded. The histologic grade was low in 33 (63%), intermediate in 18 (35%), and high in 1 (2%). All patients were treated with primary radiotherapy alone. The median dose for low-grade tumors was 3000 cGy (range 2000-4020); the median dose for intermediate and high-grade tumors was 4000 cGy (range 3000-5100). A lens-sparing approach was used in 19 patients (37%). Late complications for the lens and cornea were scored according to the subjective, objective, management, and analytic (SOMA) scale of the Late Effects of Normal Tissue (LENT) scoring system. The median follow-up was 55 months (range 6-232). RESULTS The local control rate was 100% in the 52 orbits treated. The 5-year overall survival and relapse-free survival rate was 73.6% and 65.5%, respectively. Tumor grade and location did not predict for overall survival or relapse-free survival. Seven patients (15%) developed distant recurrence (brain 2, extremity 2, mediastinum 1, liver 1, and retroperitoneum 1). One patient (2%) developed cervical node metastasis. The 5- and 10-year cataract-free survival rate was 56.7% and 32.9%, respectively. Of the 12 lens complications, 8 were LENT Grade 1 and 4 were Grade 3 toxicity. Only male gender predicted for an increased risk of cataract formation. Radiotherapy dose and technique did not predict for cataract formation; however, none of the patients who underwent the lens-sparing technique developed Grade 3 lens toxicity or required surgical correction. Of the nine corneal events, two were Grade 1, four Grade 2, and three were Grade 3 toxicity. Ten dry eyes were recorded; all were mild, and no patient had severe dry eye syndrome. Neovascular glaucoma was seen in 1 patient. No injury to the retina or optic nerve was reported. CONCLUSION Radiotherapy alone is a highly effective modality in the curative management of primary orbital lymphoma. Most complications were minimal and did not require medical or surgical intervention. Although the use of the lens-sparing technique did not influence the incidence of cataractogenesis, we continue to recommend this approach whenever possible, because our experience indicates a higher grade of toxicity occurs and a higher incidence of corrective surgery is needed in patients treated without lens protection.

Radiation-Associated Kidney Injury

The kidneys are the dose-limiting organs for radiotherapy to upper abdominal cancers and during total body irradiation. The incidence of radiotherapy-associated kidney injury is likely underreported owing to its long latency and because the toxicity is often attributed to more common causes of kidney injury. The pathophysiology of radiation injury is poorly understood. Its presentation can be acute and irreversible or subtle, with a gradual progressive dysfunction over years. A variety of dose and volume parameters have been associated with renal toxicity and are reviewed to provide treatment guidelines. The available predictive models are suboptimal and require validation. Mitigation of radiation nephropathy with angiotensin-converting enzyme inhibitors and other compounds has been shown in animal models and, more recently, in patients.

F-18 FDG PET-CT fusion in radiotherapy treatment planning for head and neck cancer.

The fusion of fluoro‐2‐deoxy‐d‐glucose–positron emission tomography (FDG‐PET) with CT scans has been shown to improve diagnostic accuracy and staging in non‐small cell lung cancer. We report on the influence of PET‐CT fusion on the management of patients with head and neck cancer.

Intracranial ependymomas: an analysis of prognostic factors and patterns of failure.

From 1965 to 1997, 49 patients were diagnosed and treated for intracranial ependymoma at one institution. Tumor location was infratentorial in two thirds, and pathology was low grade in 38 patients (78%). Gross total resection of the primary tumor was achieved in 21 (43%). Thirty-six patients received adjuvant radiotherapy; the entire neuraxis was treated in 14, whole brain in 10, and local field only in 12. Median follow-up was 9.6 years (range, 2–33 years). The 5-, 10-, and 15-year overall survival rates were 71.4%, 63.5%, and 63.5% for craniospinal radiotherapy, 60.0%, 60.0%, and 40.0% for whole brain radiotherapy, and 80.8%, 64.6%, and 64.6% for local field radiotherapy (p = 0.88). The 5-, 10-, and 15-year local control rates were 60.3%, 54.4%, and 48.9%. The prognostic factors for a better local control rate were gross total resection (p = 0.021) and low grade histology (p = 0.031). Seventeen of 43 (39.5%) M0 patients did not respond to treatment; all had local failure and 4 also had a spinal relapse. Spinal relapse developed in 3 of 31 (10%) M0 patients who did not receive spinal radiotherapy, whereas 1 of 12 (8%) who had spinal radiotherapy did not respond to treatment in the spine. The results of this study indicate that local radiotherapy is sufficient for M0 patients with intracranial ependymoma.

Results of treatment of patients with maxillary sinus carcinoma.

Information regarding results of treatment and possible prognostic factors in patients with maxillary sinus carcinoma is limited.

Esthesioneuroblastoma: The University of Iowa experience 1978-1998

Objective Esthesioneuroblastoma is rare and the best treatment has yet to be defined. The purpose of this study is to analyze the natural history, treatment, and patterns of failure of esthesioneuroblastoma treated at one institution.

Hypothyroidism in children with medulloblastoma: a comparison of 3600 and 2340 cGy craniospinal radiotherapy

PURPOSE To determine if low-dose craniospinal irradiation (2340 cGy) with chemotherapy is associated with a lower incidence of hypothyroidism compared to standard dose (3600 cGy) with or without chemotherapy in children with medulloblastoma. PATIENTS AND METHODS Between 1980 and 1999, 32 patients < or =20 years old survived after craniospinal irradiation with or without chemotherapy. Twenty patients received 3600 cGy craniospinal irradiation (CSI), whereas 12 had 2340 cGy CSI; all patients received a posterior fossa boost to a total dose 5040-5580 cGy. The median ages at the time of CSI for those receiving 2340 cGy and 3600 cGy were 7.2 and 10.2 years, respectively. Chemotherapy (CT) was employed in 22 children. All children who received 2340 cGy had CT consisting of vincristine, CCNU, and either cisplatin or cyclophosphamide. Ten of 20 (50%) patients receiving 3600 cGy had CT; the most common regimen was vincristine, CCNU, and prednisone. Serum-free thyroxine and thyroid-stimulating hormone concentrations were measured in all children at variable times after radiotherapy. Thyroid-stimulating hormone responses to i.v. thyrotrophin-releasing hormone were assessed in those suspected of having central hypothyroidism. Median follow-up for children receiving 2340 cGy was 5 years (range: 2-11.2 years), whereas for those receiving 3600 cGy, follow-up was 12.5 years (range: 2.4-20 years). RESULTS Eighteen patients (56%) developed hypothyroidism at a median time after radiotherapy of 41 months (range: 10 months to 18 years). Primary hypothyroidism was more common than central hypothyroidism (38% and 19%). All 7 children <5 years developed hypothyroidism, whereas 9 of 15 (60%) ages 5-10 and 2 of 10 (20%) age >10 years had hypothyroidism (p < 0.001). Hypothyroidism was documented in 10 of 12 (83%) who had 2340 cGy + CT, 6 of 10 (60%) who had 3600 cGy + CT, and 2 of 10 (20%) who had 3600 cGy without CT (p < 0.025). CONCLUSIONS Current treatment regimens consisting of chemotherapy and 2340 cGy craniospinal irradiation followed by a posterior fossa boost for medulloblastoma do not show a reduction of hypothyroidism. Young age and use of chemotherapy were associated with a higher incidence of hypothyroidism.

Versatility of the novalis system to deliver image-guided stereotactic body radiation therapy (SBRT) for various anatomical sites

Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) programs to treat brain tumors were implemented when we first acquired the Brainlab Novalis system in 2003. Two years later, we started an extra-cranial stereotactic radio-ablation or more appropriately a stereotactic body radiation therapy (SBRT) program using the Brainlab Novalis image-guided system at The Methodist Hospital in Houston, Texas. We hereby summarize our initial experience with this system in delivering image-guided SBRT to a total of 80 patients during our first year of clinical implementation, from February 2005 to January 2006. Over 100 lesions in more than 20 distinct anatomical sites were treated. These include all levels of spine from cervical, thoracic, lumbar, and sacral lesions. Spinal lesions encompass intramedullary, intradural, extradural, or osseous compartments. Also treated were lesions in other bony sites including orbit, clavicle, scapula, humerus, sternum, rib, femur, and pelvis (ilium, ischium, and pubis). Primary or metastatic lesions located in the head and neck, supraclavicular region, axilla, mediastinum, lung (both central and peripheral), abdominal wall, liver, kidney, para-aortic lymph nodes, prostate, and pelvis were also treated. In addition to primary radiotherapy, SBRT program using the Brainlab Novalis system allows re-irradiation for recurrence and “boost” after conventional treatment to various anatomical sites. Treating these sites safely and efficaciously requires knowledge in radiation tolerance, fraction size, total dose, biologically equivalent dose (BED), prior radiotherapy, detailed dose volume histograms (DVH) of normal tissues, and the radiosensitive/radioresistant nature of the tumor. Placement of radio-opaque markers (Visicoil, Radiomed) in anatomical sites not in close proximity to bony landmarks (e.g., kidney and liver) helps in measuring motion and providing image guidance during each treatment fraction. Tumor/organ motion data obtained using 4D-CT while the patient is immobilized in the body cast aids in planning treatment margin and determining the need for respiratory motion control, e.g., abdominal compressor, gating, or active breathing control. The inclusion of PET/CT to the Brainlab treatment planning system further refines the target delineation and possibly guides differential fraction size prescription and delivery. The majority of the patients tolerated the SBRT treatment well despite the longer daily treatment time when compared to that of conventional treatment. All patients achieved good pain relief after SBRT. Compared to conventional standard radiotherapy of lower daily fraction size, we observed that the patients achieved faster pain relief and possibly more durable symptom control. Very high local control with stable disease on imaging was observed post SBRT. Our initial experience shows that the Brainlab Novalis system is very versatile in delivering image-guided SBRT to various anatomical sites. This SBRT approach can be applied to either primary or metastatic lesions in the primary, “boost,” or re-irradiation settings. The understanding of fraction size, total dose, BED, and DVH of normal tissues is very important in the treatment planning. Appropriate use of immobilization devices, radio-opaque markers for image-guidance, 4D-CT for tumor/organ motion estimates, and fusion of planning CT scans with biological/functional imaging will further improve the planning and delivery of SBRT, hopefully leading to better treatment outcome.