Peter Chen

Image-guided helical Tomotherapy for treatment of spine tumors.

OBJECTIVES One of the most common indications for radiotherapy is treatment of the spine. The vast majority of cases are related to metastatic disease with primary tumors of the spine being rare. Conventional radiation therapy often plays an important role in the management of spine tumors although at times with significant side effects and disadvantages. Furthermore, retreatment of spine tumors is a challenge due to concerns over spinal cord toxicity. In this series, we examine the efficacy of using image-guided helical Tomotherapy and the possible advantages offered by this new technology. PATIENTS AND METHODS Eight patients at Hoag Memorial Hospital Presbyterian were treated between November 2005 and November 2006. The median age was 66 years. Of the eight patients, seven had metastatic disease with one patient having a primary neuroendocrine tumor of the spine. Five patients were previously treated to the spine with conventional radiation planning. Two patients received single fraction stereotactic radiosurgery (15 Gy) while the remaining patients received hypofractionated stereotactic radiotherapy to a median total dose of 2,500 cGy in 500 cGy fractions. RESULTS At the time of last follow-up, radiographic control was seen in all eight patients with a median local control rate of 2.5 months (range of 1-5.8 months). Four of the eight patients are still alive with median overall survival of 5.1 months (range 1.4-6.9 months). Acute toxicity ranged from Radiation Therapy Oncology Group (RTOG) score 0-2 and no patients experienced late complications of radiation myelitis. CONCLUSIONS The TomoTherapy Hi-ART system can be an alternative treatment option for upfront or retreatment of spine tumors. Minimal acute and late toxicity were seen in patients treated with Tomotherapy. Intensity-modulated radiation delivery combined with megavoltage CT image guidance offered by the TomoTherapy Hi-ART system allows for set-up and delivery accuracy that is required for stereotactic treatment of spine tumors and eliminates the need for any internal or external fiducial marker placement.

Durable Complete Response of Refractory, Progressing Metastatic Melanoma After Treatment with a Patient-Specific Vaccine

A patient with metastatic melanoma who experienced a durable complete response after treatment with a patient-specific vaccine has been described in this article. This 59-year-old woman presented with cervical spine metastases and, within the year, had experienced local disease progression and, despite various therapies, metastases to the axilla, rectum, gall bladder, and multiple soft-tissue sites. She had previously received radiation therapy, combination chemotherapy, interleukin-2 plus interferon biotherapy, and gamma knife radiosurgery, and undergone multiple surgical resections. At the time vaccine therapy was initiated, she had multiple, new, measurable, soft-tissue metastases that were increasing in size. She was treated with a vaccine consisting of autologous dendritic cells incubated with irradiated tumor cells from an autologous tumor cell line and suspended in granulocyte-macrophage colony stimulating factor (GM-CSF), with subcutaneous injections once a week for 3 weeks and monthly for 5 months. There was evidence of disease regression by the completion of therapy. A few months later a complete response was documented by radiologic scans, and subsequently reconfirmed at 6-month intervals. She remains in complete remission >2.5 years after starting the vaccine, and >2 years after completing the vaccine, and survives >4 years after her initial presentation with bone, bowel, and lymph node metastases. This is the first time she has been in a complete remission since her initial diagnosis. Patient-specific vaccines can sometimes induce durable complete regression of progressing soft-tissue melanoma metastases.

Treatment of recurrent high grade gliomas with hypofractionated stereotactic image-guided helical tomotherapy

OBJECTIVE Salvage treatment of high grade gliomas that progress after standard therapy of resection and adjuvant chemoradiation therapy includes repeat surgical resection, second line chemotherapy, re-irradiation, or often a combination of the above. We present a series on patients treated with hypofractionated stereotactic image-guided helical tomotherapy and discuss the efficacy of this new technology in the treatment of high grade gliomas. MATERIALS AND METHODS Between June 2005 and August of 2008, eight patients with recurrent high grade gliomas were treated with salvage radiation therapy using hypofractionated stereotactic image-guided helical tomotherapy after image documentation of disease progression. Median age was 48.5 years with 4 females and 4 males. Median KPS at time of treatment was 65. All patients had either Grade III or IV gliomas at time of treatment with previous history of involved field fractionated radiotherapy. Median total dose given was 2500cGy in 500cGy fractions. RESULTS The median planning target volume was 69.5cm(3). Five of the eight patients were alive at the time of last follow-up with a median survival of 7.6 months. Radiographic documented control was seen in six of the eight patients with median local control of 4.6 months. Acute Radiation Therapy Oncology Group (RTOG) toxicity scores measured zero in all patients with only one patient requiring a reoperation following treatment. CONCLUSIONS Hypofractionated stereotactic image-guided helical tomotherapy provides an alternative to other stereotactic radiation therapy and radiosurgery options for treatment of recurrent high grade gliomas.

The role of margins in extremity soft tissue sarcoma.

For extremity soft tissue sarcomas, limb salvage is now standard of care. The extent of surgical margins is balanced with functionality of the resected limb. Although negative margins are the goal, the necessary width is unclear. Additional considerations for margin adequacy include presence of anatomic barriers such as fascia and periosteum, proximity of critical structures, receipt of adjuvant and neoadjuvant therapies, and histologic subtype. Multidisciplinary team discussion is critical for treatment planning. J. Surg. Oncol. 2016;113:333–338.

Oncoplastic Split Reduction with Intraoperative Radiation Therapy

A standard Wise-pattern reduction can be used to excise a breast cancer that falls within the Wise pattern.1 When the tumor is located outside the Wise pattern, it can be removed by tunneling and pulling the lesion through the Wise-pattern incision. When it is necessary to take skin overlying the tumor, the Wise pattern can be reconfigured by moving either the lower inner or lower outer quadrant triangles, which are a normal part of the standard Wise pattern, to a position over the tumor. This change must be accompanied by splitting the vertical limb of the reduction to accommodate the repositioning of the triangle, a technique known as split reduction.2 This alteration in the Wise pattern removes the skin directly over the tumor and guarantees that the anterior margin will be clear. Intraoperative radiation therapy (IORT) is a technique used for administering a single dose of radiation therapy given during a ‘lumpectomy’ procedure. Two prospective, randomized trials have shown that, in selected low-risk patients, IORT may be adequate as the entire course of radiation therapy.3,4 In this video, we combined IORT with a split reduction tumor excision.

Acute and Chronic Complications in Patients with Ductal Carcinoma in Situ Treated with Intraoperative Radiation Therapy

Intraoperative radiation therapy (IORT) delivers radiation therapy directly to the tumor bed at the time of surgery. Minimal data are available regarding IORT complications in patients diagnosed with ductal carcinoma in situ (DCIS) using the Xoft® Axxent eBx® System. 146 patients with pure DCIS received X‐ray based IORT therapy using the Xoft® Axxent eBx® System at Hoag Memorial Hospital Presbyterian between June 2010 to April 2016 and were accrued to an IORT data registry study. The protocols were approved by the institutional review board and met the guidelines of their responsible governmental agency. Data were collected at 1 week, 1 month, 6 months, 1 year, and thereafter yearly. Acute complications were defined as those occurring within the first month. Chronic complications were those that persisted beyond 6 months. Acute complications were observed in 18% of patients and included hematomas that required drainage, an infection treated with antibiotics, and erythema. Chronic complications were observed in 12% of patients and included a seroma, fibrosis and hyperpigmentation. The majority of acute and chronic problems were mild (Grade I). If Grade I erythema, fibrosis, and hyperpigmentation are not included, only 11/146 patients (7.5%) had significant complications. The rate of acute and chronic complications from X‐ray IORT in DCIS patients was low compared to historical toxicity rates observed in DCIS patients treated with whole breast irradiation. Our data indicate that X‐ray IORT can be utilized safely in patients diagnosed with DCIS.

Recent advances in the management of liposarcoma

Liposarcoma is the most common soft tissue sarcoma. With its various subtypes, the natural history of this disease can vary significantly from a locally recurrent tumor to a highly malignant one carrying a poor prognosis. Progress in the understanding of the specific molecular abnormalities in liposarcoma provides greater opportunity for new treatment modalities. Although surgical resection and radiation therapy remain the keystones for the management of primary liposarcoma, the inclusion of novel agents that target known abnormalities in advanced liposarcoma enhances the potential for improved outcomes.

A retrospective study of induction chemotherapy with docetaxel, cisplatinum, and 5-fluorouracil followed by concurrent radiotherapy with cetuximab in locally advanced head and neck cancer.

BACKGROUND The objective was to study the results of induction chemotherapy followed by external beam radiation therapy with concurrent cetuximab in the treatment of locally advanced head and neck cancer. METHODS Seventeen patients with stage III or IV squamous cell carcinomas of the head and neck who received docetaxel, cisplatinum, and 5-fluorouracil followed by radiation therapy with concurrent cetuximab were retrospectively analyzed. All radiation was delivered with image-guided intensity-modulated radiation treatments. Primary end points analyzed were local control and overall survival. RESULTS With a median follow-up of 17 months, the approximate 2-year local control was 85%, with overall survival being 91%. At time of last follow-up, only 1 death was observed, with the cause of death unknown. Two local failures were observed, and the patients were under active management for their recurrences at time of last follow-up. No distant metastatic failures were noted among the patients. CONCLUSIONS Induction chemotherapy with docetaxel, cisplatinum, and 5-fluorouracil followed by concurrent radiation with cetuximab provides for excellent locoregional control of disease. Future prospective studies can better establish the efficacy of this treatment regimen to current favored protocols.

Central neurocytoma: case report of an 81-year-old and histopathologic findings.

Central Neurocytomas are rare and usually benign tumors found primarily in the lateral ventricles of the brain. Central Neurocytomas are composed of uniform round cells exhibiting neuronal differentiation and are found almost exclusively in young adults between 15 and 60 years of age. The authors report the case of an 81-year-old man with a history of severe psychosis and depression, who presented with progressive confusion and ataxia likely unrelated to a central neurocytoma of his right lateral ventricle. The patient underwent a stereotactic biopsy of the lesion, followed by Gamma Knife radiosurgery. Histopathology showed immunohistological staining for synaptophysin, neuron specific enolase (NSE) and neuronal nuclear antigen (NeuN). A review of published literature on central neurocytomas revealed that this tumor occurs most frequently in young adults with a median age between 25 and 30 years. This pathology has never been reported in patients over the age of 80. Gamma Knife radiosurgery was successful in decreasing the tumor volume by 20% at the four month follow-up, but the fact that the patient died of unrelated occurrences in the elderly cannot be ruled out. Patients with central neurocytomas commonly present with obstructive hydrocephalus and immediate treatment may be necessary to tide over urgent situations.

Upfront boost Gamma Knife “leading-edge” radiosurgery to FLAIR MRI–defined tumor migration pathways in 174 patients with glioblastoma multiforme: a 15-year assessment of a novel therapy

OBJECTIVE Glioblastoma multiforme (GBM) is composed of cells that migrate through the brain along predictable white matter pathways. Targeting white matter pathways adjacent to, and leading away from, the original contrast-enhancing tumor site (termed leading-edge radiosurgery [LERS]) with single-fraction stereotactic radiosurgery as a boost to standard therapy could limit the spread of glioma cells and improve clinical outcomes. METHODS Between December 2000 and May 2016, after an initial diagnosis of GBM and prior to or during standard radiation therapy and carmustine or temozolomide chemotherapy, 174 patients treated with radiosurgery to the leading edge (LE) of tumor cell migration were reviewed. The LE was defined as a region outside the contrast-enhancing tumor nidus, defined by FLAIR MRI. The median age of patients was 59 years (range 22-87 years). Patients underwent LERS a median of 18 days from original diagnosis. The median target volume of 48.5 cm3 (range 2.5-220.0 cm3) of LE tissue was targeted using a median dose of 8 Gy (range 6-14 Gy) at the 50% isodose line. RESULTS The median overall survival was 23 months (mean 43 months) from diagnosis. The 2-, 3-, 5-, 7-, and 10-year actual overall survival rates after LERS were 39%, 26%, 16%, 10%, and 4%, respectively. Nine percent of patients developed treatment-related imaging-documented changes due to LERS. Nineteen percent of patients were hospitalized for management of edema, 22% for resection of a tumor cyst or new tumor bulk, and 2% for shunting to treat hydrocephalus throughout the course of their disease. Of the patients still alive, Karnofsky Performance Scale scores remained stable in 90% of patients and decreased by 1-3 grades in 10% due to symptomatic treatment-related imaging changes. CONCLUSIONS LERS is a safe and effective upfront adjunctive therapy for patients with newly diagnosed GBM. Limitations of this study include a single-center experience and single-institution determination of the LE tumor target. Use of a leading-edge calculation algorithm will be described to achieve a consistent approach to defining the LE target for general use. A multicenter trial will further elucidate its value in the treatment of GBM.