Douglas Einstein

Diagnosis and Treatment of Melanoma Brain Metastasis: A Literature Review

BACKGROUND Brain metastasis is common in patients with malignant melanoma and represents a significant cause of morbidity and mortality. Nearly 37% of patients with malignant melanoma eventually develop brain metastasis, and autopsy reports show that 75% of those who died of this disease developed brain metastasis. METHODS We review the level I and level II evidence that guides indications for treatment with surgery, stereotactic radiosurgery, chemotherapy, and immunotherapy for patients with melanoma brain metastasis. RESULTS Level I evidence supports the role of whole brain radiotherapy, microsurgery, and radiosurgery alone or in combination for the treatment of patients with melanoma brain metastasis. Chemotherapy has been ineffective. Ongoing studies continue to assess the effects of immunotherapy and agents in development. CONCLUSIONS Brain metastasis is a common and formidable challenge in patients with malignant melanoma. Although there have been no randomized controlled trials exclusively in patients with melanoma brain metastasis, care can be guided by the application of level I evidence for the treatment of brain metastasis in general and phase II studies focusing specifically on melanoma brain metastasis. Promising new agents and approaches are needed and will hopefully be identified in the near future.

Stereotactic Body Radiation Therapy for Nonresectable Tumors of the Pancreas

BACKGROUND Stereotactic body radiation therapy (SBRT) has emerged as a potential treatment option for local tumor control of primary malignancies of the pancreas. We report on our experience with SBRT in patients with pancreatic adenocarcinoma who were found not to be candidates for surgical resection. METHODS The prospective database of the first 20 consecutive patients receiving SBRT for unresectable pancreatic adenocarcinomas and a neuroendocrine tumor under an IRB approved protocol was reviewed. Prior to SBRT, cylindrical solid gold fiducial markers were placed within or around the tumor endoscopically (n = 13), surgically (n = 4), or percutaneously under computerized tomography (CT)-guidance (n = 3) to allow for tracking of tumor during therapy. Mean radiation dose was 25 Gray (Gy) (range 22-30 Gy) delivered over 1-3 fractions. Chemotherapy was given to 68% of patients in various schedules/timing. RESULTS Patients had a mean gross tumor volume of 57.2 cm(3) (range 10.1-118 cm(3)) before SBRT. The mean total gross tumor volume reduction at 3 and 6 mo after SBRT were 21% and 38%, respectively (P < 0.05). Median follow-up was 14.57 mo (range 5-23 mo). The overall rate of freedom from local progression at 6 and 12 mo were 88% and 65%. The probability of overall survival at 6 and 12 mo were 89% and 56%. No patient had a complication related to fiducial markers placement regardless of modality. The rate of radiation-induced adverse events was: grade 1-2 (11%) and grade 3 (16%). There were no grade 4/5 adverse events seen. CONCLUSION Our preliminary results showed SBRT as a safe and likely effective local treatment modality for pancreatic primary malignancy with acceptable rate of adverse events.

Phase II Trial of Radiosurgery to Magnetic Resonance Spectroscopy-Defined High-Risk Tumor Volumes in Patients With Glioblastoma Multiforme

PURPOSE To determine the efficacy of a Gamma Knife stereotactic radiosurgery (SRS) boost to areas of high risk determined by magnetic resonance spectroscopy (MRS) functional imaging in addition to standard radiotherapy for patients with glioblastoma (GBM). METHODS AND MATERIALS Thirty-five patients in this prospective Phase II trial underwent surgical resection or biopsy for a GBM followed by SRS directed toward areas of MRS-determined high biological activity within 2 cm of the postoperative enhancing surgical bed. The MRS regions were determined by identifying those voxels within the postoperative T2 magnetic resonance imaging volume that contained an elevated choline/N-acetylaspartate ratio in excess of 2:1. These voxels were marked, digitally fused with the SRS planning magnetic resonance image, targeted with an 8-mm isocenter per voxel, and treated using Radiation Therapy Oncology Group SRS dose guidelines. All patients then received conformal radiotherapy to a total dose of 60 Gy in 2-Gy daily fractions. The primary endpoint was overall survival. RESULTS The median survival for the entire cohort was 15.8 months. With 75% of recursive partitioning analysis (RPA) Class 3 patients still alive 18 months after treatment, the median survival for RPA Class 3 has not yet been reached. The median survivals for RPA Class 4, 5, and 6 patients were 18.7, 12.5, and 3.9 months, respectively, compared with Radiation Therapy Oncology Group radiotherapy-alone historical control survivals of 11.1, 8.9, and 4.6 months. For the 16 of 35 patients who received concurrent temozolomide in addition to protocol radiotherapeutic treatment, the median survival was 20.8 months, compared with European Organization for Research and Treatment of Cancer historical controls of 14.6 months using radiotherapy and temozolomide. Grade 3/4 toxicities possibly attributable to treatment were 11%. CONCLUSIONS This represents the first prospective trial using selective MRS-targeted functional SRS combined with radiotherapy for patients with GBM. This treatment is feasible, with acceptable toxicity and patient survivals higher than in historical controls. This study can form the basis for a multicenter, randomized trial.

Treatment of glomus jugulare tumors in patients with advanced age: planned limited surgical resection followed by staged gamma knife radiosurgery: a preliminary report.

Objective: To minimize treatment comorbidities in glomus jugulare tumor patients with advanced age while reducing pulsatile tinnitus and preserving or improving residual hearing using a limited middle ear/mastoid tumor resection and postoperative gamma knife radiosurgery to tumor remnants in the jugular foramen region. Study Design: Retrospective consecutive case review of five patients. Setting: Tertiary referral, academic medical center. Patients: Patients with advanced age (mean, 69.6 yr; range, 61-78 yr) harboring symptomatic glomus jugulare tumors. Intervention: All patients were treated with resection of middle ear and mastoid portions of tumor and subsequent gamma knife radiosurgery to jugular foramen portion of tumor. Main Outcome Measures: Length of hospitalization; hearing, pulsatile tinnitus, cranial nerve, and tumor control status. Results: All patients were treated on an outpatient surgical basis without the need for blood transfusion. There were no incidents of a change in cranial nerve status (Cranial Nerves VII, IX, X, XI, and XII) in the immediate postoperative period. All patients had improvement or resolution of pulsatile tinnitus with preservation or improvement of preoperative hearing levels. Tumor volume was stable or reduced in all patients at mean follow-up of 19 months (range, 11-24 mo). Gamma knife radiosurgery (mean peripheral dose of 15 Gy) was not associated with any significant immediate or delayed complications. Conclusion: Short-term data reveals that staged microsurgical and radiosurgical therapy for glomus jugulare tumors in the symptomatic patient with advanced age is safe and yields favorable results regarding tinnitus, hearing, and cranial nerve status. Long-term data are needed to further evaluate the effectiveness of this treatment algorithm before extrapolating this treatment option to younger patients.

Cyberknife stereotactic body radiation therapy for nonresectable tumors of the liver: preliminary results.

Purpose. Stereotactic body radiation therapy (SBRT) has emerged as a treatment option for local tumor control of primary and secondary malignancies of the liver. We report on our updated experience with SBRT in patients with non-resectable tumors of the liver. Methods. Our first 17 consecutive patients (mean age 58.1 years) receiving SBRT for HCC (n = 6), IHC (n = 3), and LM (n = 8) are presented. Mean radiation dose was 34Gy delivered over 1–3 fractions. Results. Treated patients had a mean decrease in maximum pretreatment tumor diameter from 6.9 ± 4.6 cm to 5.0 ± 2.1 cm at three months after treatment (P < .05). The mean total tumor volume reduction was 44% at six months (P < .05). 82% of all patients (14/17) achieved local control with a median follow-up of 8 months. 100% of patients with HCC (n = 6) achieved local control. Patients with surgically placed fiducial markers had no complications related to marker placement. Conclusion. Our preliminary results showed that SBRT is a safe and effective local treatment modality in selected patients with liver malignancies with minimal adverse events. Further studies are needed to define its role in the management of these malignancies.

Quality of coverage: Conformity measures for stereotactic radiosurgery

In radiosurgery, conformity indices are often used to compare competing plans, evaluate treatment techniques, and assess clinical complications. Several different indices have been reported to measure the conformity of the prescription isodose to the target volume. The PITV recommended in the Radiation Therapy Oncology Group (RTOG) radiosurgery guidelines, defined as the ratio of the prescription isodose volume (PI) over the target volume (TV), is probably the most frequently quoted. However, these currently used conformity indices depend on target size and shape complexity. The objectives of this study are to systematically investigate the influence of target size and shape complexity on existing conformity indices, and to propose a different conformity index–the conformity distance index (CDI). The CDI is defined as the average distance between the target and the prescription isodose line. This study examines five case groups with volumes of 0.3, 1.0, 3.0, 10.0, and 30.0 cm3. Each case group includes four simulated shapes: a sphere, a moderate ellipsoid, an extreme ellipsoid, and a concave “C” shape. Prescription dose coverages are generated for three simplified clinical scenarios, i.e., the PI completely covers the TV with 1 and 2 mm margins, and the PI over‐covers one half of the TV with a 1 mm margin and under‐covers the other half with a 1 mm margin. Existing conformity indices and the CDI are calculated for these five case groups as well as seven clinical cases. When these values are compared, the RTOG PITV conformity index and other similar conformity measures have much higher values than the CDI for smaller and more complex shapes. With the same quality of prescription dose coverage, the CDI yields a consistent conformity measure. For the seven clinical cases, we also find that the same PITV values can be associated with very different conformity qualities while the CDI predicts the conformity quality accurately. In summary, the proposed CDI provides more consistent and accurate conformity measurements for all target sizes and shapes studied, and therefore will be a more useful conformity index for irregularly shaped targets. PACS number(s): 87.90.+y, 87.53.Ly

Stereotactic Body Radiosurgery for Pelvic Relapse of Gynecologic Malignancies

Clinical management of pelvic relapses from gynecologic malignancies remains challenging. Bulky pelvic relapses often lead to symptomatic cancer-related complications and poor clinical outcomes. Options may be limited by prior surgical, chemotherapeutic, and radiation treatment. Stereotactic body radiosurgery is a novel treatment modality which allows high radiation dose delivery in a non-coplanar fashion with sub-millimeter precision utilizing a linear accelerator mounted on a robotic arm. This study details our clinical experience with stereotactic body radiosurgery for treatment of patients with pelvic relapses of gynecologic malignancies after prior pelvic radiation.

Staged Gamma Knife Radiosurgery after Tailored Surgical Resection

Object: Although benign and slow growing, glomus jugulare tumors can be locally aggressive because of their proximity to lower cranial nerves and major vascular structures. Surgical resection frequently leads to complications, and radiosurgery alone often does not relieve symptoms. We report a novel treatment paradigm of tailored surgical resection followed by staged radiosurgery that allows for tissue diagnosis and immediate improvement of symptoms and tumor control without the morbidity of radical surgical resection. Methods: Five patients with glomus jugulare tumors and contraindications to extensive surgery each underwent an outpatient otologic procedure to resect the portion of the tumor in the middle ear and mastoid with no attempt to remove tumor in the jugular bulb. Each patient returned 2–5 months later for Gamma Knife radiosurgery to the remainder of the tumor, which consisted of one 15-Gy dose prescribed to the 50% isodose curve. Patients were followed through outpatient visits and surveillance MR imaging for up to 3 years. Results: All patients were successfully treated as outpatients. Each had improvement or resolution of pulsatile tinnitus and otalgia and preserved or improved hearing. One patient developed a delayed facial palsy prior to radiosurgery that resolved completely; there were no other changes in cranial nerve function after either procedure. Tumor volume was stable or reduced in all patients at most recent follow-up, and there were no immediate or delayed complications. Conclusions: Staged outpatient microsurgical and radiosurgical therapy for glomus jugulare tumors in the symptomatic patient is safe and yields favorable results regarding tumor size, tinnitus, hearing and cranial nerve status.

Cyberknife Radiosurgery for Squamous Cell Carcinoma of Vulva after Prior Pelvic Radiation Therapy

Limited options exist for patients experiencing a local recurrence of vulvar malignancies after surgery and pelvic radiation. These recurrences often are associated with cancer-related skin desquamation and poor clinical outcomes. A new radiotherapeutic treatment modality for the previously irradiated patient is cyberknife radiosurgery, which uses a linear accelerator mounted on an industrial robotic arm to allow non-coplanar radiation therapy delivery with sub-millimeter precision. This study describes the first reported use of cyberknife radiosurgery for the treatment of recurrent vulvar cancer in three women.

The Impact of a Negative 111Indium-Capromab Pendetide Scan Before Salvage Radiotherapy

PURPOSE We determined the prognostic role, if any, of the ProstaScint (111)indium-capromab pendetide scan before salvage radiotherapy for biochemical recurrence after RP for localized prostate cancer. MATERIALS AND METHODS We reviewed the records of 649 patients who underwent a ProstaScint scan from 1998 to 2004. A total of 44 patients were identified who had biochemical recurrence after RP and underwent a ProstaScint scan immediately before salvage radiotherapy. All patients received salvage radiotherapy to the prostatic bed unless pelvic lymph node uptake was identified on the scan, resulting in initial whole pelvic radiotherapy with 45 Gy, followed by a conformal boost to the prostate bed in 6. The median salvage radiotherapy dose to the prostate bed was 72 Gy. Patient demographics, pathological information, PSA values and ProstaScint results were collected retrospectively. The majority of ProstaScint scans were digitally fused with noncontrast pelvic computerized tomography images for interpretation. PSA progression after radiotherapy was defined using American Society for Therapeutic Radiation and Oncology criteria. RESULTS At a mean followup of 22 months 43 of 44 patients (97%) experienced a PSA decrease after salvage radiotherapy with a mean PSA nadir of 0.16 ng/ml compared to a mean pre-radiotherapy PSA of 1.7 ng/ml. Of the 44 patients 15 (34%) showed post-radiotherapy PSA progression. When the entire cohort was analyzed, patients with negative ProstaScint scans had statistically lower post-radiotherapy PSA progression rates than patients with positive scans (1 of 10 or 10% vs 14 of 34 or 41%, p = 0.026). Patients with negative ProstaScint results were also statistically more likely to have a pre-radiotherapy PSA of less than 1.0 ng/ml (p = 0.005), no seminal vesicle involvement (p = 0.006), a greater mean PSA doubling time (p = 0.008) and received no hormone therapy (p = 0.003). When patients with pre-radiotherapy PSA less than 1.0 ng/ml were analyzed, a negative ProstaScint scan suggested but did not provide a statistically significant advantage over pre-radiotherapy PSA alone for predicting post-radiotherapy PSA progression (1 of 9 or 11% for negative vs 5 of 15 or 33% for positive scans, p = 0.20). CONCLUSIONS Our early experience supports an improved prognosis in patients receiving salvage pelvic radiotherapy for biochemical recurrence after RP who have a negative pre-radiotherapy ProstaScint scan. However, this finding is not necessarily independent of pre-radiotherapy PSA.