Intramedullary Metastases to Conus Medullaris: A Review of the Literature with a Case Illustration.

Introduction: Intramedullary metastases to the conus medullaris spinalis (IMCM) pose a rare problem in neurosurgical oncology and are usually encountered as a complicated clinical scenario in the setting of advanced systemic malignancy with poor overall survival. Despite the progress in interdisciplinary oncological care, their management remains complicated. Research Question: We performed a PRISMA-guided literature search to achieve a pooled analysis of all previously reported IMCM cases that contained detailed clinical data on this problem to investigate the currently employed management options and respective outcomes. We obtained a clinical vignette and performed a comprehensive narrative review of IMCM management. Materials and Methods: The PubMed/MEDLINE/Google Scholar, Cochrane and Embase databases were systematically searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All relevant publications retrieved were subjected to full-text analysis in detail and pertinent information was extracted. Results: The most common systemic primary tumor site as the origin of IMCM was the lung, followed by the breast. Overall, the pooled median survival was 6 months (range 0.5-36 months). Patients who received both surgery and radiation therapy had the longest overall survival (OS) (mean 9.9 months) and those who received no oncological treatment (neither surgery nor adjuvant therapy) had the shortest OS (mean 3.6 months). In cases where surgical resection was performed as part of the treatment plan for metastases, those with partial tumor resection had a more favorable neurological outcome than patients who underwent aggressive gross total resection. Conclusions: Based on the results of our analysis, we find that diligent microsurgical resection (subtotal or total) followed by radiation therapy appears as an effective and suitable treatment in select patients with IMCM. When surgery is not feasible as part of the treatment algorithm, radiation therapy alone (conventional or radiosurgery) also appears to be a suitable treatment option that confers a benefit to the patient.

Ablative radiotherapy improves survival but does not cure autochthonous mouse models of prostate and colorectal cancer.

BACKGROUND: Genetically engineered mouse models (GEMMs) of cancer are powerful tools to study mechanisms of disease progression and therapy response, yet little is known about how these models respond to multimodality therapy used in patients. Radiation therapy (RT) is frequently used to treat localized cancers with curative intent, delay progression of oligometastases, and palliate symptoms of metastatic disease. METHODS: Here we report the development, testing, and validation of a platform to immobilize and target tumors in mice with stereotactic ablative RT (SART). Xenograft and autochthonous tumor models were treated with hypofractionated ablative doses of radiotherapy. RESULTS: We demonstrate that hypofractionated regimens used in clinical practice can be effectively delivered in mouse models. SART alters tumor stroma and the immune environment, improves survival in GEMMs of primary prostate and colorectal cancer, and synergizes with androgen deprivation in prostate cancer. Complete pathologic responses were achieved in xenograft models, but not in GEMMs. CONCLUSIONS: While SART is capable of fully ablating xenografts, it is unable to completely eradicate disease in GEMMs, arguing that resistance to potentially curative therapy can be modeled in GEMMs.

Mice can be used to model the types of cancer seen in people to investigate the effects of cancer therapies, such as radiation. Here, we apply radiation therapy treatments that are able to cure cancer in humans to mice that have cancer of the prostate or colorectum. We show that the mice do not experience many side effects and that the tumours reduce in size, but in some cases show progression after treatment. Our study demonstrates that mice can be used to better understand how human cancers respond to radiation treatment, which can lead to the development of improved treatments and treatment schedules.

Reduced Mortality Risk in the Recent Era in Early-Stage Hodgkin Lymphoma Patients Treated With Radiation Therapy With or Without Chemotherapy.

PURPOSE: To determine the effect of treatment changes over time on all-cause mortality risk in patients with early-stage Hodgkin lymphoma (HL) after radiation therapy. The long-term survivorship of those with HL necessitates quantification of the late risk of mortality from HL and other causes. METHODS AND MATERIALS: An institutional review board-approved retrospective study was conducted using a multi-institutional database of 1541 stage I and II HL patients treated from 1968 to 2007 with radiation therapy alone or combined-modality treatment. The analytic methods included cumulative incidence function, Kaplan-Meier estimates and log-rank tests for overall survival (OS) differences, and Cox proportional hazards modeling. RESULTS: The median age at diagnosis was 27 years. At a median follow-up of 15.2 years (35% of patients with >20 years of follow-up), 395 patients had died of all causes, including 85 HL, 168 second malignancy (25 hematologic and 143 nonhematologic), 70 cardiovascular, and 21 pulmonary deaths. The cumulative incidence of non-HL mortality had surpassed HL mortality at 8.3 years. For patients treated from 1968 to 1982, 1983 to 1992, and 1993 to 2007, the 15-year OS rates were 78%, 85%, and 88%, respectively (P=.0016). On Cox proportional hazards analysis, age, B symptoms, and number of disease sites were significantly associated with all-cause mortality in the first decade of follow-up, with a trend toward significance for radiation field extent. CONCLUSIONS: The all-cause mortality risk was significantly lower for patients treated in the most recent era during the first decade of follow-up, likely due to improved HL therapy resulting in a higher cure rate and lower treatment-related toxicity from smaller radiation fields. Current efforts toward radiation treatment reduction might further reduce the long-term mortality risk for these patients.

Bending the cost curve: a unique collaboration between radiation oncologists and Blue Cross Blue Shield of Massachusetts to optimize the use of advanced technology.

PURPOSE: Intensity-modulated radiation therapy (IMRT) limits the dose of radiation to critical normal tissue structures and can be applied to the management of most cancers treated with radiation therapy. Because of increased treatment planning time and quality assurance, IMRT is costly. Blue Cross Blue Shield of Massachusetts (BCBSMA) and the Massachusetts Radiation Oncology Physicians Advisory Council (PAC) developed a strategy to develop standards for the appropriate use of IMRT. METHODS: Normal tissue volume guidelines were established in multiple oncology disease areas and body site regions. Guidelines were activated in September 2011, and the use of IMRT per case was tracked quarterly by BCBSMA staff. RESULTS: During the first year of activation of the volume-based guidelines, use of IMRT decreased by 17% in Massachusetts, in contrast to a 20% increase during the previous year. CONCLUSIONS: The normal tissue-based guidelines have decreased the use of IMRT in Massachusetts; increased the use of 3D treatment; continued communication between treating radiation oncologists and an insurance organization responsible for cost and quality in medicine; increased cost savings; enabled an efficient appeal process; and provided optimal, cost-effective patient care. This may prove to be an effective model for other disciplines and other developing and maturing radiation technologies.

Thyroid malignancies in survivors of Hodgkin lymphoma.

PURPOSE: To quantify the incidence of thyroid cancer after Hodgkin lymphoma (HL) and determine disease characteristics, risk factors, and treatment outcomes. METHODS AND MATERIALS: Thyroid cancer cases were retrospectively identified from a multi-institutional database of 1981 HL patients treated between 1969 and 2008. Thyroid cancer risk factors were evaluated by a Poisson regression model. RESULTS: With a median follow-up duration of 14.3 years (range, 0-41.2 years), 28 patients (1.4%) developed a thyroid malignancy. The overall incidence rate (expressed as the number of cases per 10,000 person-years) and 10-year cumulative incidence of thyroid cancer were 9.6 and 0.26%, respectively. There were no observed cases of thyroid malignancy in patients who received neck irradiation for HL after age 35 years. Age <20 years at HL diagnosis and female sex were significantly associated with thyroid cancer. The incidence rates of females aged <20 at HL diagnosis in the first 10 years, ≥10 years, ≥15 years, and ≥20 years after treatment were 5, 31, 61, and 75 cases per 10,000 person-years of follow-up, respectively. At a median follow-up of 3.5 years after the thyroid cancer diagnosis, 26 patients (93%) were alive without disease, 1 (4%) was alive with metastatic disease, and 1 (4%) died of metastatic disease, at 6 and 3.6 years after the thyroid cancer diagnosis, respectively. CONCLUSIONS: Although HL survivors have an increased risk for thyroid cancer, the overall incidence is low. Routine thyroid cancer screening may benefit females treated at a young age and ≥10 years from HL treatment owing to their higher risk, which increases over time.

Cellular and molecular chaperone fusion vaccines: targeting resistant cancer cell populations.

Molecular chaperone-based vaccines offer a number of advantages for cancer treatment. We have discussed the deployment of a vaccine prepared by gentle isolation of Hsp70 from tumour dendritic cell fusions (Hsp70 fusion vaccine). The vaccine was highly effective in triggering specific T cell immunity and in the treatment of tumour-bearing mice and the preparation was shown to retain an increased amount of tumour antigens compared to other chaperone-based isolates. This approach has the further advantage that tumour sub-populations could be used to prepare the Hsp70 fusion vaccine. Cellular fusion vaccines were made to specifically target drug-resistant cancer cells and tumour cell populations enriched in ovarian cancer stem cells (CSC). Such vaccines showed enhanced capacity to trigger T cell immunity to these resistant ovarian carcinoma populations. We have discussed the potential of using the cellular and Hsp70 fusion vaccine approaches in therapy of treatment-resistant cancer cells and its deployment in combination with ionising radiation or hyperthermia to enhance the effectiveness of both forms of therapy.

Heat shock proteins, autoimmunity, and cancer treatment.

Heat shock proteins (HSPs) have been linked to the therapy of both cancer and inflammatory diseases, approaches that utilize contrasting immune properties of these proteins. It would appear that HSP family members Hsp60 and Hsp70, whether from external sources or induced locally during inflammation, can be processed by antigen-presenting cells and that HSP-derived epitopes then activate regulatory T cells and suppress inflammatory diseases. These effects also extend to the HSP-rich environments of cancer cells where elevated HSP concentrations may participate in the immunosuppressive tumor milieu. However, HSPs can also be important mediators of tumor immunity. Due to their molecular chaperone properties, some HSPs can bind tumor-specific peptides and deliver them deep into the antigen-processing pathways of antigen-presenting cells (APCs). In this context, HSP-based vaccines can activate tumor-specific immunity, trigger the proliferation and CTL capabilities of cancer-specific CD8+ T cells, and inhibit tumor growth. Further advances in HSP-based anticancer immunotherapy appear to involve improving the properties of the molecular chaperone vaccines by enhancing their antigen-binding properties and combating the immunosuppressive tumor milieu to permit programming of active CTL capable of penetrating the tumor milieu and specifically targeting tumor cells.

Frameless angiogram-based stereotactic radiosurgery for treatment of arteriovenous malformations.

PURPOSE: Stereotactic radiosurgery (SRS) is an effective alternative to microsurgical resection or embolization for definitive treatment of arteriovenous malformations (AVMs). Digital subtraction angiography (DSA) is the gold standard for pretreatment diagnosis and characterization of vascular anatomy, but requires rigid frame (skull) immobilization when used in combination with SRS. With the advent of advanced proton and image-guided photon delivery systems, SRS treatment is increasingly migrating to frameless platforms, which are incompatible with frame-based DSA. Without DSA as the primary image, target definition may be less than optimal, in some cases precluding the ability to treat with a frameless system. This article reports a novel solution. METHODS AND MATERIALS: Fiducial markers are implanted into the patient's skull before angiography. Angiography is performed according to the standard clinical protocol, but, in contrast to the previous practice, without the rigid frame. Separate images of a specially designed localizer box are subsequently obtained. A target volume projected on DSA can be transferred to the localizer system in three dimensions, and in turn be transferred to multiple CT slices using the implanted fiducials. Combined with other imaging modalities, this "virtual frame" approach yields a highly precise treatment plan that can be delivered by frameless SRS technologies. RESULTS: Phantom measurements for point and volume targets have been performed. The overall uncertainty of placing a point target to CT is 0.4 mm. For volume targets, deviation of the transformed contour from the target CT image is within 0.6 mm. The algorithm and software are robust. The method has been applied clinically, with reliable results. CONCLUSIONS: A novel and reproducible method for frameless SRS of AVMs has been developed that enables the use of DSA without the requirement for rigid immobilization. Multiple pairs of DSA can be used for better conformality. Further improvement, including using nonimplanted fiducials, is potentially feasible.

Heat shock proteins and cancer vaccines: developments in the past decade and chaperoning in the decade to come.

Molecular chaperone-peptide complexes extracted from tumors (heat shock protein [HSP] vaccines) have been intensively studied in the preceding two decades, proving to be safe and effective in treating a number of malignant diseases. They offer personalized therapy and target a cross-section of antigens expressed in patients' tumors. Future advances may rely on understanding the molecular underpinnings of this approach to immunotherapy. One property common to HSP vaccines is the ability to stimulate antigen uptake by scavenger receptors on the antigen-presenting cell surface and trigger T-lymphocyte activation. HSPs can also induce signaling through Toll-Like receptors in a range of immune cells and this may mediate the effectiveness of vaccines.

The role of heat shock factors in stress-induced transcription.

Heat shock proteins (HSPs) are rapidly induced after stresses, such as heat shock, and accumulate at high concentrations in cells. HSP induction involves a family of heat shock transcription factors that bind the heat shock elements of the HSP genes and mediate transcription in trans. We discuss methods for the study of HSP binding to HSP promoters and the consequent increases in HSP gene expression in vitro and in vivo.

Clinically significant cardiac disease in patients with Hodgkin lymphoma treated with mediastinal irradiation.

This study assessed the cumulative incidence of clinically significant cardiac disease in 1279 Hodgkin lymphoma patients treated with mediastinal irradiation and quantified the standard incidence ratios (SIRs) and absolute excess risks of cardiac procedures compared with a normal matched population. Cox regression analysis was used to explore factors associated with cardiac complications. Poisson regression analysis of SIRs was used to estimate the excess risk of cardiac interventions from mediastinal irradiation. After a median follow-up of 14.7 years, 187 patients experienced 636 cardiac events and 89 patients required a cardiac procedure. 5-, 10-, 15-, and 20-year cumulative incidence rates of cardiac events were 2.2%, 4.5%, 9.6%, and 16%. SIRs for cardiac procedures were increased for coronary artery bypass graft (3.19), percutaneous intervention (1.55), implantable cardioverter defibrillator or pacemaker placement (1.9), valve surgery (9.19), and pericardial surgery (12.91). Absolute excess risks were 18.2, 19.3, 9.4, 14.1, and 4.7 per 10 000 person-years, respectively. Older age at diagnosis and male sex were predictors for cardiac events. However, younger age at diagnosis was associated with excess risk specifically from radiation therapy compared with the general population. These results may help guideline development for both the types and timing of cardiac surveillance in survivors of Hodgkin lymphoma.

Early-stage, lymphocyte-predominant Hodgkin's lymphoma: patient outcomes from a large, single-institution series with long follow-up.

PURPOSE The optimal treatment for early-stage, lymphocyte-predominant Hodgkin's lymphoma (LPHL) is not well defined. Treatment has become less aggressive over time in an attempt to reduce iatrogenic complications, such as cardiac mortality and second cancers, but long-term efficacy is unclear. We present the long-term outcome of patients treated at a single institution. PATIENTS AND METHODS The study population includes 113 patients with stage I or II LPHL treated between 1970 and 2005. Pathologic diagnosis for all patients was confirmed using standard criteria. Ninety-three patients received radiation therapy (RT) alone, 13 received RT with chemotherapy, and seven received chemotherapy alone. Among patients treated with RT, 25 received limited-field, 35 received regional-field, and 46 received extended-field RT. Results Median follow-up was 136 months. Ten-year progression-free survival (PFS) rates were 85% (stage I) and 61% (stage II); overall survival (OS) rates were 94% and 97% for stages I and II, respectively. PFS and OS did not differ among patients who received limited-field, regional-field, or extended-field RT. In contrast, six of seven patients who received chemotherapy alone without RT developed early disease progression and required salvage treatment. Multivariable analysis adjusting for extent of RT, clinical stage, sex, and use of chemotherapy confirmed that the extent of RT was not significantly associated with PFS (P = .67) or OS (P = .99). The addition of chemotherapy to RT did not improve PFS or OS compared with RT alone. CONCLUSION RT alone leads to sustained disease control and high long-term survival rates in patients with early-stage LPHL. This study supports the use of limited-field RT alone to treat this disease.

Lung dose-volume parameters and the risk of pneumonitis for patients treated with accelerated partial-breast irradiation using three-dimensional conformal radiotherapy.

PURPOSE: There are no data on how complication rates after accelerated partial-breast irradiation delivered by three-dimensional conformal radiotherapy are affected by treatment technique. We therefore examined the risk of pneumonitis in relation to lung dose-volume parameters. PATIENTS AND METHODS: Our prospective dose-escalation trial enrolled 198 treated patients from 2003 to 2007. Patients received 32 or 36 Gy in 4-Gy fractions, given twice daily: 29 (14%) were treated with pure photons; 149 (77%) with mixed photons and electrons; and 20 (10%) with protons. RESULTS: There were four cases of pneumonitis at 4, 4, 7, and 9 months after treatment. All were in the 36-Gy cohort and were treated with pure photons. The risk of pneumonitis for the two cohorts combined was: 17% (four of 24) for an ipsilateral lung volume (ILV) receiving 20 Gy or higher (ILV, 20 Gy) of 3% or higher (P = .0002 for comparison to ILV 20 Gy < 3%, Fisher's exact test); 20% (four of 20) for an ILV 10 Gy of 10% or higher (P = .0001); and 15% (four of 26) for an ILV 5 Gy of 20% or higher (P = .0002). CONCLUSION: The risk of pneumonitis appeared related to the ILV treated. This volume can be reduced by using mixed photons and electron when possible. We recommend that the ILV 20 Gy should be lower than 3%, the ILV 10 Gy lower than 10%, and the ILV 5 Gy lower than 20% when purely coplanar techniques are used.

A prospective study of salivary gland function in lymphoma patients receiving head and neck irradiation.

PURPOSE: To determine the radiation dose-response relationship on salivary dysfunction and quality of life (QOL) over time in patients with lymphoma receiving radiation therapy (RT) to the head and neck (H&N). METHODS AND MATERIALS: We conducted a prospective study on salivary-gland function in lymphoma patients receiving RT to the H&N. Fifteen patients were enrolled on the study. Dose-volume histograms and mean doses to the salivary glands were generated. Radiation-related toxicities and H&N-specific QOL were assessed before treatment and at prespecified time points posttreatment. Factors predicting a decrement in QOL were explored using Fisher's exact test. RESULTS: During RT, 47% of patients experienced Grade >or= 2 acute toxicity of the salivary gland, mucous membrane, or both. QOL scores improved over time, but up to one third of patients continued to have persistent oral symptoms at 2 years. At 6 months, a mean dose to at least one of the parotids of > 31 Gy was significantly associated with persistent dry mouth (100% vs. 17%, p = 0.02) and sticky saliva (100% vs. 25%, p = 0.04); a mean dose of > 11 Gy to the minor salivary glands was significantly associated with persistent sticky saliva (100% vs. 25%, p = 0.04), although the difference was no longer significant at 1 year. CONCLUSIONS: Limiting the mean parotid dose to

Targeting the oncogene and kinome chaperone CDC37.

CDC37 is a molecular chaperone that physically stabilizes the catalytic domains found in protein kinases and is therefore a wide-spectrum regulator of protein phosphorylation. It is also an overexpressed oncoprotein that mediates carcinogenesis by stabilizing the compromised structures of mutant and/or overexpressed oncogenic kinases. Recent work shows that such dependency of malignant cells on increased CDC37 expression is a vulnerability that can be targeted in cancer by agents that deplete or inhibit CDC37. CDC37 is thus a candidate for broad-spectrum molecular cancer therapy.

Organ deformation and dose coverage in robotic respiratory-tracking radiotherapy.

PURPOSE: Respiratory motion presents a significant challenge in stereotactic body radiosurgery. Respiratory tracking that follows the translational movement of the internal fiducials minimizes the uncertainties in dose delivery. However, the effect of deformation, defined as any changes in the body and organs relative to the center of fiducials, remains unanswered. This study investigated this problem and a possible solution. METHODS AND MATERIALS: Dose delivery using a robotic respiratory-tracking system was studied with clinical data. Each treatment plan was designed with the computed tomography scan in the end-expiration phase. The planned beams were applied to the computed tomography scan in end-inspiration following the shift of the fiducials. The dose coverage was compared with the initial plan, and the uncertainty due to the deformation was estimated. A necessary margin from the clinical target volume to the planning target volume was determined to account for this and other sources of uncertainty. RESULTS: We studied 12 lung and 5 upper abdomen lesions. Our results demonstrated that for lung patients with properly implanted fiducials a 3-mm margin is required to compensate for the deformation and a 5-mm margin is required to compensate for all uncertainties. Our results for the upper abdomen tumors were still preliminary but indicated a similar result, although a larger margin might be required. CONCLUSION: The effect of body deformation was studied. We found that adequate dose coverage for lung tumors can be ensured with proper fiducial placement and a 5-mm planning target volume margin. This approach is more practical and effective than a recent proposal to combine four-dimensional planning with respiratory tracking.

Targeting Cdc37 inhibits multiple signaling pathways and induces growth arrest in prostate cancer cells.

Members of the 90-kDa heat shock protein (HSP90) family are known to bind and stabilize intermediates in a wide variety of cell signaling pathways and contribute to their dysregulation in cancer. An important intracellular cofactor for HSP90 is Cdc37, a protein with a broad role in fostering the activities of protein kinases. By targeting Cdc37 using RNA interference, we have shown that the loss of Cdc37 function induces irreversible growth arrest in androgen receptor-positive and -negative prostate carcinoma cells. In contrast to HSP90-directed agents, Cdc37 targeting seems to affect cancer cells through a distinct mechanism and does not significantly deplete the intracellular levels of most known HSP90 client proteins. Instead, Cdc37 depletion inhibits cellular kinase activity and flux through growth-promoting signal transduction cascades. We show that the loss of Cdc37 leads to reduced activity of the Erk, Akt, mTOR, and androgen-induced pathways. We have also discovered synergistic interactions between Cdc37 inactivation and the HSP90-inhibitory anticancer drug 17-(allylamino)-17-demethoxygeldanamycin (17AAG). These interactions involve enhanced degradation of proteins essential for growth and inhibition of 17AAG-induced expression of the antiapoptotic HSP70. Thus, Cdc37 is essential for maintaining prostate tumor cell growth and may represent a novel target in the search for multitargeted therapies based on the HSP90 chaperone system.

Mechanisms for Hsp70 secretion: crossing membranes without a leader.

Heat shock protein 70 (Hsp70) is released from cells of many types and plays a significant signaling role, particularly in the inflammatory and immune responses. However, Hsp70 does not contain a consensus secretory signal and thus cannot traverse the plasma membrane by conventional mechanisms. However, Hsp70 can be released from cells by active mechanism that are independent of de novo Hsp70 synthesis or cell death. This pathway is similar to one utilized by the leaderless protein interleukin 1beta. Hsp70 release involves transit through an endolysosomal compartment and is inhibited by lysosomotropic compounds. In addition, the rate of Hsp70 secretion correlates well with the appearance of the lysosomal marker LAMP1 on the cell surface, further suggesting the role for endolysosomes. The entry of Hsp70 into this secretory compartment appears to involve the ABC-family transporter proteins. While the cell signals involved in triggering Hsp70 release through this lysosomal pathway are largely unknown, recent data suggest a regulatory role for extracellular ATP. These mechanisms are also shared by interleukin 1beta secretion. Following release it has been shown that Hsp70 binds to adjacent cells, suggesting that the secreted protein participates in paracrine or autocrine interactions with adjacent cell surfaces. Thus an outline is beginning to of the mechanisms of Hsp70 secretion. Much further study will be required to fully elucidate mechanisms involved in targeting Hsp70 towards the non-canonical secretion pathways and its regulation.

Academic career selection and retention in radiation oncology: the Joint Center for Radiation Therapy experience.

PURPOSE: The United States healthcare system has witnessed declining reimbursement and increasing documentation requirements for longer than 10 years. These have decreased the time available to academic faculty for teaching and mentorship. The impact of these changes on the career choices of residents is unknown. The purpose of this report was to determine whether changes have occurred during the past decade in the proportion of radiation oncology trainees from a single institution entering and staying in academic medicine. METHODS AND MATERIALS: We performed a review of the resident employment experience of Harvard Joint Center for Radiation Therapy residents graduating during 13 recent consecutive years (n = 48 residents). The outcomes analyzed were the initial selection of an academic vs. nonacademic career and career changes during the first 3 years after graduation. RESULTS: Of the 48 residents, 65% pursued an academic career immediately after graduation, and 44% remained in academics at the last follow-up, after a median of 6 years. A later graduation year was associated with a decrease in the proportion of graduates immediately entering academic medicine (odds ratio, 0.78; 95% confidence interval, 0.65-0.94). However, the retention rate at 3 years of those who did immediately enter academics increased with a later graduation year (p = 0.03). CONCLUSION: During a period marked by notable changes in the academic healthcare environment, the proportion of graduating Harvard Joint Center for Radiation Therapy residents pursuing academic careers has been declining; however, despite this decline, the retention rates in academia have increased.

Long-term outcome and mortality trends in early-stage, Grade 1-2 follicular lymphoma treated with radiation therapy.

PURPOSE: To analyze long-term outcomes and causes of death in patients receiving radiation therapy (RT) for localized, low-grade follicular lymphoma. METHODS AND MATERIALS: Between 1972 and 2000, 106 patients with Stage I-II, Grade 1-2 follicular lymphoma received RT alone or radiation and chemotherapy (RT/CT). Seventy-four percent had Stage I, and 26% had Stage II disease. Seventy-six percent received RT alone, and 24% received combined RT/CT. Second malignancy rates were compared with an age- and sex-matched population. RESULTS: Median follow-up was 12 years. Median survival time was 19 years. The 5-, 10-, and 15-year overall survival (OS) rates were 93%, 75%, and 62%, respectively. Age > or = 60 was the only significant adverse prognostic factor with respect to OS. There were 35 deaths, 20 of which were attributable to lymphoma. Freedom from treatment failure (FFTF) rates at 5, 10, and 15 years were 72%, 46%, and 39%, respectively. Forty-seven patients (48%) relapsed. Tumor size > 3 cm was the only significant adverse factor for FFTF. Observed incidence of second malignancy did not significantly exceed expected incidence. CONCLUSIONS: Although patients with early-stage, low-grade follicular lymphoma have long median survival, the leading cause of death remains lymphoma. However, patients receiving RT do not have significantly elevated cumulative incidence of second malignancy.