Combined Modality Approach Research Articles

Predicting biochemical tumor control after brachytherapy for clinically localized prostate cancer: The Memorial Sloan-Kettering Cancer Center experience

PurposeTo identify predictors of biochemical tumor control and present an updated prognostic nomogram for patients with clinically localized prostate cancer treated with brachytherapy. Methods and MaterialsOne thousand four hundred sixty-six patients with clinically localized prostate cancer were treated with brachytherapy alone or along with supplemental conformal radiotherapy. Nine hundred one patients (61%) were treated with Iodine-125 (125I) monotherapy to a prescribed dose of 144Gy, and 41 (4.5%) were treated with Palladium-103 (103Pd) monotherapy to a prescribed dose of 125Gy. In patients with higher risk features (n=715), a combined modality approach was used, which comprised 125I or 103Pd seed implantation or Iridium-192 high–dose rate brachytherapy followed 1–2 months later by supplemental intensity-modulated image-guided radiotherapy to the prostate. ResultsThe 5-year prostate-specific antigen relapse-free survival (PSA-RFS) outcomes for favorable-, intermediate-, and high-risk patients were 98%, 95%, and 80%, respectively (p<0.001). Multivariate Cox regression analysis identified Gleason score (p<0.001) and pretreatment PSA (p=0.04) as predictors for PSA tumor control. In this cohort of patients, the use of neoadjuvant and concurrent androgen deprivation therapy did not influence biochemical tumor control outcomes. In the subset of patients treated with 125I monotherapy, D90>140Gy compared with lower doses was associated with improved PSA-RFS. A nomogram predicting PSA-RFS was developed based on these predictors and had a concordance index of 0.70. ConclusionsResults with brachytherapy for all treatment groups were excellent. D90 higher than 140Gy was associated with improved biochemical tumor control compared with lower doses. Androgen deprivation therapy use did not impact on tumor control outcomes in these patients.

Hodgkin's lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

D. A. Eichenauer1, A. Engert1, M. Andre2, M. Federico3, T. Illidge4, M. Hutchings5, & M. Ladetto6 on behalf of the ESMO Guidelines Working Group* First Department of Internal Medicine, University Hospital Cologne and German Hodgkin Study Group (GHSG), Cologne, Germany; CHU Dinant-Godinne, UCL Namur, Yvoir, Belgium; Department of Oncology, Hematology and Respiratory Diseases, University of Modena and Reggio Emilia, Modena, Italy; Institute of Cancer Sciences, University of Manchester, Manchester, UK; Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Divisione di Ematologia, Azienda Ospedaliera Santi Antonio e Biagio e Cesare Arrigo, Alessandria, Italy

Prostate Cancer

Prostate cancer is the most commonly diagnosed noncutaneous malignancy in men in the United States. This chapter discusses the epidemiology, pathogenesis, and diagnosis of prostate cancer, as well as risk factors, the use of digital rectal examination and prostate-specific antigen measurement for screening, and staging for the disease. Also reviewed are the natural history of untreated prostate cancer; the treatment of localized and advanced prostate cancer, including prostatectomy, radiation therapy, and androgen deprivation therapy; and the prevention of prostate cancer. Figures illustrate the incidence rates of prostate cancer by race, age-adjusted and/or age-specific cancer of the prostate, the risk of a diagnosis in 20 years (based on being cancer free at certain ages), the 5-year survival rate, and the overall survival in patients with early prostate cancer treated with observation or radical prostatectomy. Tables in this chapter review the clinical staging definitions and the combined-modality staging approach to prostate cancer. This chapter contains 116 references.

Current therapeutic strategies for invasive and metastatic bladder cancer.

BackgroundBladder cancer is one of the most common cancers in Europe, the United States, and Northern African countries. Muscle-invasive bladder cancer is an aggressive epithelial tumor, with a high rate of early systemic dissemination. Superficial, noninvasive bladder cancer can most often be cured; a good proportion of invasive cases can also be cured by a combined modality approach of surgery, chemotherapy, and radiation. Recurrences are common and mostly manifest as metastatic disease. Those with distant metastatic disease can sometime achieve partial or complete remission with combination chemotherapy.Recent developmentsBetter understanding of the biology of the disease has led to the incorporation of molecular and genetic features along with factors such as tumor grade, lympho-vascular invasion, and aberrant histology, thereby allowing identification of ‘favorable’ and ‘unfavorable’ cancers which helps a more accurate informed and objective selection of patients who would benefit from neoadjuvant and adjuvant chemotherapy. Gene expression profiling has been used to find molecular signature patterns that can potentially be predictive of drug sensitivity and metastasis. Understanding the molecular pathways of invasive bladder cancer has led to clinical investigation of several targeted therapeutics such as anti-angiogenics, mTOR inhibitors, and anti-EGFR agents.ConclusionWith improvements in the understanding of the biology of bladder cancer, clinical trials studying novel and targeted agents alone or in combination with chemotherapy have increased the armamentarium for the treatment of bladder cancer. Although the novel biomarkers and gene expression profiles have been shown to provide important predictive and prognostic information and are anticipated to be incorporated in clinical decision-making, their exact utility and relevance calls for a larger prospective validation.

Broad antigenic coverage induced by vaccination with virus-based cDNA libraries cures established tumors

We show here that a cDNA library of normal tissue, expressed from a highly immunogenic viral platform, cures established tumors of the same histological type from which the cDNA library was derived. With suboptimal vaccination, immune escape was possible, but only when tumor cells were forced to acquire a radically new phenotype, readily treated by second line therapy. This approach has several major advantages. Use of the cDNA library leads to presentation of a broad repertoire of (undefined) tumor associated antigens, which reduces emergence of treatment resistant variants and also permits implementation of rational, combined modality approaches in the clinic. Finally, the viral vectors can be delivered systemically, without the need for tumor targeting, and are amenable to clinical grade production. Therefore, virus-expressed cDNA libraries represent a novel paradigm for cancer treatment by addressing many of the key issues which have undermined the efficacy of immuno/virotherapy to date.

Phase II trial of neoadjuvant pemetrexed plus cisplatin followed by surgery and radiation in the treatment of malignant pleural mesothelioma (MPM).

7090 Background: Combined modality approaches to therapy, including surgery (S) and radiation, have proved feasible and are becoming one of the standards of care in MPM. This study was designed to assess the efficacy of the combination of neoadjuvant pemetrexed+cisplatin, extrapleural pneumonectomy (EPP) and hemithoracic radiation (HTR) (trimodality [TM] therapy) in MPM. Methods: This was a multicenter, phase II, open-label study with event-free survival (EFS) (defined as time from enrollment to first observation of disease progression, death due to any cause or early treatment discontinuation) as the primary endpoint. Between 2005 and 2008, 56 patients (pts) with MPM (T1-3, N0-2) were screened, of whom 54 were enrolled (87% male; median age 63 [range 39-75] years; ECOG PS 0-1; adequate organ function). Pre-operative pemetrexed 500 mg/m2+cisplatin 75 mg/m2 IV was given every 21 days x 3 cycles, plus folic acid, vitamin B12 and dexamethasone, followed by EPP and HTR (total dose 54 Gy). After 2 deaths due to cardiopulmonary failure, occurred after HTR therapy (21 [38.8%] pts out of 54 were already enrolled in the study at this time), the protocol was amended reducing HTR dose to 50.4 Gy. Results: Of the 54 pts enrolled, 52 (96.3%) completed chemotherapy (CT), 45 (83.3%) underwent S, 22 (40.7%) completed the whole treatment including 90 day follow up. The median EFS was 6.9 months (95%CI: 5.0–10.5) and the median progression-free survival was 8.6 months (95%CI: 6.3-14.4). A total of 18 (33.3%) and 13 (24.1%) pts were still event free after 1 and 2 years respectively. Of the 54 pts, 16 (29.6%) showed partial response to CT, 31 (57.4%) showed stable disease, 4 (7.4%) showed progression, responses in 3 (5.6%) pts were unknown (overall response before S). During the whole study 36 (66.7%) pts experienced ≥1 grade 3-4 toxicity (the most frequent were hematological and gastrointestinal) but no statistically significant differences were observed before and after amendment. Conclusions: These results are aligned with the available scientific literature related to the TM approach on MPM, showing that the adopted multidisciplinary treatment is effective with a manageable toxicity profile.

Medical Treatment of Mesothelioma: Anything New?

In the present report, we review the current standard and investigational treatments of malignant pleural mesothelioma (MPM). Several studies have reported the use of gemcitabine and cisplatin as an induction chemotherapy in combination with extrapleural pneumonectomy (EPP) and thoracic radiation in a combined-modality approach for resectable MPM. Since the combination of cisplatin with pemetrexed was applied as the standard first-line regimen for unresectable MPM, the combination as an induction chemotherapy regimen has been proven effective in phase 2 trials. In addition, intensity-modulated radiation therapy and proton therapy have been introduced as new radiation methods into the combined modality. Hyperthermic intraoperative chemotherapy following EPP appears effective with acceptable toxicity. In addition, clinical studies that include molecular targeting agents, immunotherapy, and gene therapy have all been conducted. Thus, although there are numerous hopeful treatments for MPM, the benefits of these regimens remain to be proven in a randomized clinical setting.

Palliative Hypofractionated Radiotherapy For Non-Small Cell Lung Cancer (NSCLC) Patients Previously Treated By Induction Chemotherapy: Is It For Many, Some, All, Or None?

pproximatelyis 30% of patients with non-smallpatients with adequate performance status, many disease that surgically unresectable (1). In current practice guidelines recommend that these patients be treated with a combination of chemotherapy and external beam irradiation (2). Over the last several years, the use of chemotherapy with radiation has been supported by several phase III multi-institutional randomized studies, with patients diagnosed with locally advanced NSCLC, having a better progression-free (PFS) and overall survival (OS) when treated with combination therapy than with radiation alone (3, 4). Despite improvements in outcome, results remain modest with aggressive combined modality therapy, with 2 and 5 year survivals in the range of 30% and 20%, respectively (4, 5). In addition, these combined modality approaches are associated with significant toxicity in a patient population that in many cases is already limited in terms of functional reserve before they even initiate definitive therapy. Despite curative efforts, many patients have disease progression or are overly symptomatic either from treatment or from their disease. It could be argued that for certain locally advanced patients, aggressive systemic and local treatment causes more harm than good.

Enhancement of photodynamic therapy by 2,5-dimethyl celecoxib, a non-cyclooxygenase-2 inhibitor analog of celecoxib

Photodynamic therapy (PDT) effectiveness can be improved by employing combined modality approaches involving pharmaceuticals targeting the tumor microenvironment and/or tumor cell death pathways. In one approach, combining PDT with celecoxib improves long-term tumoricidal activity without increasing normal tissue photosensitization. However, side effects arising from the use of coxib based cyclooxygenase-2 (COX-2) inhibitors, including cardiovascular injury, decreases the clinical applications of this class of compounds. A growing number of studies demonstrate that the tumoricidal actions of coxibs such as celecoxib involve non-COX-2 mediated mechanisms. The celecoxib analog, 2,5-dimethyl celecoxib (DMC), lacks COX-2 inhibitory activity but exhibits cytotoxic properties comparable to the COX-2 inhibitor celecoxib. We compared the effectiveness of DMC and celecoxib in modulating PDT response at both the in vitro and in vivo level using a C3H/BA murine mammary carcinoma model. Both DMC and celecoxib blocked PDT induced expression of the pro-survival protein survivin, enhanced the endoplasmic reticulum stress (ERS) response of PDT, and increased both apoptosis and cytotoxicity in BA cells exposed to combination protocols. DMC enhanced the in vivo tumoricidal responsiveness of PDT without altering PGE 2 levels. Our data demonstrates that DMC improved PDT by increasing apoptosis and tumoricidal activity without modulating COX-2 catalytic activity. Our results also suggest that celecoxib mediated enhancement of PDT may involve both COX-2 dependent and independent mechanisms.

Combined modality approaches in the management of adult glioblastoma.

Over the past two decades, management of newly diagnosed glioblastoma has undergone significant evolution. While surgery has long been a mainstay of management for this disease, and while radiotherapy has a proven survival role, initial efforts at radiotherapy dose escalation, use of radiosurgery, brachytherapy, and altered fractionation did not improve patient survival. Recently, multiple modality therapy integrating maximal safe resection, postoperative radiation, and new systemic therapies have resulted in improved patient outcomes compared with older regimens utilizing surgery and postoperative radiation alone. Numerous trials are currently underway investigating the combination of surgery, radiation, and systemic therapy with targeted agents to find ways to further improve outcomes for adults with glioblastoma.

Renal Cell Cancer: What Can We Learn from Pre-Operative Studies?

Renal cell carcinoma (RCC) affects approximately 60,000 people in Europe and in the United States each year (Ferlay et al., 2007; Jemal et al., 2010), and is associated with high rates of morbidity and mortality. The incidence of RCC is rising, perhaps because of the widespread use of abdominal imaging, resulting in an increased detection of small renal masses, and surgical intervention for these (Hollingsworth et al., 2006; Falebita et al., 2009). Surgery remains an integral part of the management of RCC, and is the only curative treatment in patients with disease confined to the kidney and its regional vasculature and lymph nodes. However, about 30% of patients are diagnosed with metastatic renal cell carcinoma (mRCC) at presentation (Motzer et al., 1996) and a similar proportion will later develop metastases (Leibovich et al., 2003). Until 2007, a combination of cytoreductive nephrectomy (CN) and immunotherapy, usually interferon-α, was considered to be the standard of care for those patients presenting with mRCC deemed fit enough, although cytokine therapy was associated with modest benefits and much toxicity (Coppin et al., 2005). The basis for nephrectomy in the context of metastatic disease was provided by two similar prospective trials which randomized patients to CN plus interferon or interferon alone. Combined analysis of the two trials demonstrated a median survival of 13.6 months for surgery plus interferon, and 7.8 months for interferon alone (HR = 0.69, 95% CI = 0.55–0.87, p = 0.002; Flanigan et al., 2004). The simplest rationale for why CN might improve survival in mRCC is a reduction in overall tumor burden, thus delaying time to a lethal burden of disease; other theories include a decrease in the amount of tumor shedding and systemic signaling from the primary renal mass, effective palliation of pain, bleeding and paraneoplastic syndromes, and removal of a source of significant immunosuppression. The latter was proposed on the basis of reports of spontaneous regression in mRCC, which occurs very rarely, but this phenomenon was also observed in series when surgery was not performed (Russo and O'Brien, 2008). Despite the evidence for a combined modality approach to mRCC in the cytokine era, these agents did not improve clinical outcomes when studied in the adjuvant setting (Pizzocaro et al., 2001; Messing et al., 2003; Atzpodien et al., 2005), and were not tested as neoadjuvant treatment due to their side effects and the very limited response rates observed in the primary tumors.

Neoadjuvant radiotherapy for locally advanced and high-risk prostate cancer

Men presenting with high-risk or locally advanced prostate cancer may benefit from a combination of radiotherapy and surgery to maximize local control. Adjuvant radiotherapy following surgery has improved biochemical progression-free survival, metastasis-free survival, lengthened the time to hormone therapy use and improved overall survival in three randomized-phase III trials. One surprising result of the Southwest Oncology Group (SWOG) 8794 trial and the European Organisation for Research and Treatment of Cancer (EORTC) 22911 trial is that treatment failure was mainly a result of lack of local control. This finding has led to a new appreciation of local control as a determinant of survival and the role for combined modality approaches within a multidisciplinary team in the treatment of high-risk and locally advanced prostate cancer. One emerging novel approach is the use of preoperative or intraoperative radiotherapy in addition to best surgical and systemic treatments. Preliminary results from clinical trials indicate low rates of intraoperative toxic effects, an advantage of short treatment times and smaller image-guided radiotherapy treatment volumes when compared with postoperative radiotherapy. Potential disadvantages include over-treatment of patients and lack of data on long-term toxic effects. We present the published treatment approaches and rational for preoperative and intraoperative radiotherapy and compare these methods to the utility of postoperative radiotherapy.

Management of relapsed and refractory classical Hodgkin lymphoma in children and adolescents

There are a number of options for salvage treatment in children and adolescents with relapsed and refractory classical Hodgkin Lymphoma. These include salvage with standard dose chemotherapy, high dose chemotherapy with autologous stem cell transplant, allogeneic stem cell transplant or other novel approach. Radiotherapy has an important role in the salvage of some patients as part of a combined modality approach. This review outlines these salvage approaches and discusses whether the evidence from paediatric studies justifies a risk-adapted approach to salvage for individual patients or whether all patients should receive consolidation with high dose chemotherapy and autologous stem cell transplantation, which is often described as standard salvage management in adults. The important prognostic factors and how these may be used to allocate patients to standard versus high dose chemotherapy regimens are discussed. The role of allogeneic transplantation, novel agents and late effects will also be discussed.

Secondary MDS/AML In Hodgkin Lymphoma Patients Treated within German Hodgkin Study Group (GHSG) Clinical Trials After Introduction of the BEACOPP Protocol

AbstractAbstract 2682 Background:With modern multi-agent chemotherapy regimens optionally combined with radiotherapy, even patients with advanced Hodgkin lymphoma (HL) are cured in over 80% of cases. Since there is only little room for further therapeutic improvements, one major focus of current clinical research in HL consists in reducing treatment-related late effects such as secondary malignancies. Secondary MDS/AML represents a relevant problem since it was reported to be associated with a very poor prognosis. To shed some more light on incidence, course and outcome of patients with secondary MDS/AML after HL treatment, we performed an analysis addressing this issue. Patients treated within German Hodgkin Study Group (GHSG) clinical trials after introduction of the BEACOPP protocol were included. Methods and patients:11891 HL patients of all stages aged 16 to 75 and treated within the third (HD7-HD9, 1993–1998), fourth (HD10-HD12, 1998–2003) and fifth (HD13-HD15, 2003–2009) GHSG trial generation, the BEACOPP14 pilot study (1997-2000) and a phase II trial evaluating the role of GnRH analogues and oral contraceptives in female patients receiving BEACOPPescalated were retrospectively analyzed. Treatment consisted of radiotherapy alone, chemotherapy alone or combined-modality approaches. Results:With a median follow-up of 70 months, overall secondary MDS/AML rate was 0.8% (99 patients). However, 13 patients had a concurrent event (i.e. progress/relapse of HL or another secondary malignancy requiring salvage treatment) prior to MDS/AML diagnosis so that 86 patients were included in the present analyses. Median time from HL treatment to MDS/AML diagnosis was 28.3 months. The median age of patients developing secondary MDS/AML was significantly higher than the median age in the whole patient group (41 vs 34 years, p=.0002). To determine the impact of treatment intensity on the risk to develop secondary MDS/AML, patients were assigned into three groups. Groups consisted of patients who had received no BEACOPP-containing treatment, less than four cycles of BEACOPPescalated and four or more cycles of BEACOPPesclated, respectively. As a result, patients receiving four or more cycles of BEACOPPescalated had a significantly increased risk to develop secondary MDS/AML when compared to the other groups (5-year cumulative incidence 1.5% vs 0.5% and 0.3%, respectively, log-rank p<.0001). In 36 patients included in this analysis, allogeneic stem cell transplantation (aSCT) was applied to treat secondary MDS/AML. Patients who received aSCT had a significantly lower median age than those treated with conventional chemotherapy or supportive care only (35 vs 50 years, p=.0016) and showed an improved outcome. However, median overall survival (OS) after MDS/AML diagnosis was only 7.2 months. Conclusions:Secondary MDS/AML is a relevant problem after HL therapy particularly in patients diagnosed with advanced stages treated with intensive first-line protocols. However, the clinical benefit achieved by the use of these more intensive protocols clearly outweighs the risk of developing secondary MDS/AML. To reduce the risk of developing secondary MDS/AML, novel treatment strategies should include risk-adapted early treatment stratification based on modern tools such as positron emission tomography (PET) to prevent overtreatment whenever possible. Disclosures:No relevant conflicts of interest to declare.

Outcome of Patients with Advanced Hodgkin Lymphoma Who Are Either Refractory to or Relapsed After Primary Therapy with the Stanford V Regimen

AbstractAbstract 4828 Purpose:Stanford V is an abbreviated combined modality approach for the treatment of advanced stage Hodgkin lymphoma (HL). This regimen was developed with the aim of shortening the duration of chemotherapy, limiting the radiotherapy (RT) to a modified involved field and thereby potentially reducing short and long term toxicity while maintaining or improving cure rates. Specifically the chemotherapy regimen has significantly lower cumulative doses of adriamycin, bleomycin and alkylating agents compared to other standard regimens such as ABVD or escalated BEACOPP. We have previously reported excellent outcomes with this regimen with a freedom from progression (FFP) of 89% and overall survival (OS) of 96% (Horning, S.J., et al., J Clin Oncol 2002, 20:630-7). The purpose of this study was to determine the outcome of patients (pts) treated with secondary therapy after failing Stanford V. Methods:Pts with advanced stage HL who had either refractory disease or had relapsed after primary therapy with Stanford V, were retrospectively identified from the HL database. We analyzed this group of patients for risk factors, salvage therapy, and treatment outcome. Results:Between May 1989 and March 2003, 167 pts were treated on protocol. At a median follow-up of 12.8 years the outcomes are excellent with a 10-year FFP and OS of 87% and 93%, respectively. Therapy failed in 19 pts (11%) of which 16 relapsed and 3 did not complete the intended treatment (disease progression n=2, and muscle pain and hyponatremia n=1). The median age of pts who failed therapy was 31 years (range 21 – 58) with a median time to progression of 5.1 months (range 0.2 – 41.4). 11 pts relapsed at 0 to 12 months from completion of therapy and 8 pts relapsed at > 12 months. At initial diagnosis 5 had stage I/II disease with bulky mediastinum, 5 stage III and 9 stage IV disease. The International Prognostic Score (IPS) at initial diagnosis was 0–1 (n=4), 2–3 (n=10) and 4–7 (n=5). 13/19 (68%) pts relapsed outside the RT field, 2 infield, 3 both infield and outside and 1 unknown. 7/19 pts in whom therapy failed had bulky disease and of these 5 failed outside the RT field. Relapse was detected clinically in 12 pts, and on surveillance positron emission tomography scan performed every 3 to 6 months in 5 pts who were asymptomatic (2 pts unknown). 14/19 (74%) pts received secondary therapy with a platinum-containing regimen (ICE or DHAP) with an overall response rate (ORR) of 91% (complete response [CR] n=1, partial response [PR] n=9, progressive disease [PD] n=1, unknown response n=3), followed by an autologous hematopoietic stem cell transplant. 5 pts were treated with non-transplant regimens consisting of chemotherapy with MOPP/ABV + RT (n=2), ChlVPP (n=1), oral cyclophosphamide (n=1) and procarbazine/alkeran/adriamycin/etoposide (n=1), with an ORR of 80% (CR n=4). Reasons for non-transplant therapy were neuropathy (n=1), pt preference (n=1), liver disease (n=1), and unknown (n=2). 11 of the 19 pts in whom Stanford V failed died (disease progression n=3, second malignancy n=2, graft failure n=1, infection n=1, liver failure n=1, cardiac arrest n=1, suicide n=1 and unknown n=1). At a median follow-up of 8 years, the disease-specific survival (DSS), FFP and OS for pts with refractory or relapsed disease after Stanford V was 84%, 63% and 42%, respectively. Outcome of pts who relapsed within a year was worse than pts who relapsed > 1 year with an OS of 36% versus 50%, respectively. There was no difference in FFP for these groups, 64% versus 63%, respectively. Conclusions:The outcome of pts with advanced HL is excellent with the Stanford V regimen. For the 11% of pts in whom front line therapy fails, secondary therapy is effective with a DSS of > 80%. The majority of pts (84%) failed at distant sites suggesting that more aggressive upfront chemotherapy may have been beneficial in these pts. Future efforts will aim at identifying this subset upfront. Pts who relapse within a year have a worse outcome despite salvage and for this subgroup, newer therapies are warranted. Disclosures:Horning: Genentech: Employment.

Role of Radiotherapy in Modern Treatment of Hodgkin's Lymphoma

Hodgkin's Lymphoma was incurable until the advent of effective therapeutic radiation around the first half of the 20th century. As survival rates improved, the long-term toxicities from radiotherapy began to emerge. This together with the availability of effective chemotherapy has encouraged a combined modality approach for early-staged disease and the omission of radiotherapy in advanced-staged disease. The differing toxicities of radiotherapy and chemotherapy has promoted ongoing research to identify the utility of each of these modalities in the modern management of Hodgkin's Lymphoma. This article will provide a critical review of the developments and indications for modern radiotherapy, in context with advances in chemotherapy, for the treatment of Hodgkin's Lymphoma.

Polyostotic Sclerosing Histiocytosis (Erdheim-Chester Disease) Treated with Combined Vertebroplasty and Radiation Therapy

Erdheim-Chester disease is an uncommon form of non-Langherans-cell histiocytosis, with a heterogeneous range of systemic manifestations and a pattern of typical clinico-pathological and radiological features. Symmetric sclerotic radiological alterations of the long bones are peculiar, such as the infiltration of several organs by lipid-laden histiocytes. Radiation therapy has been anecdotally employed in a palliative setting in order to relieve symptoms mainly due to cerebral, retro-orbital and skeletal localizations. Exclusive osseous involvement is rarely described in the medical literature. Moreover, the role, timing and schedule of radiotherapy in this subset of patients remain controversial. We herein report on a case of osseous-only Erdheim-Chester disease treated with a combined modality approach including transoral vertebroplasty and external beam radiation therapy, which gave an analgesic effect that lasted 1 year, with no treatment-related side effects.

Intergroup randomized phase III study of androgen deprivation therapy (ADT) plus radiation therapy (RT) in locally advanced prostate cancer (CaP) (NCIC-CTG, SWOG, MRC-UK, INT: T94-0110; NCT00002633).

CRA4504 Background: The impact of radiotherapy on overall survival (OS) in men with locally advanced CaP is unclear. The SPCG-7 trial recently showed a benefit to RT for CaP specific mortality. Our primary objective was to assess the effect of RT on OS when added to lifelong ADT in men with locally advanced CaP. Methods: Patients with T3/T4 (1057) or T2, PSA &gt; 40 μ g/l (119) or T2 PSA &gt; 20 μ g/l and Gleason ≥ 8 (25) and N0 /NX, M0 prostate adenocarcinoma were randomized to lifelong ADT (bilateral orchiectomy or LHRH agonist) with or without RT (65-69 Gy to prostate ± seminal vesicles with or without 45Gy to pelvic nodes). The primary endpoint was OS and secondary endpoints included disease specific survival (DSS), time to disease progression and quality of life. Results: 1205 patients were randomized from 1995 to 2005, 602 to ADT and 603 to ADT+RT (well balanced with respect to baseline characteristics). A protocol specified second interim analysis on OS was performed in Aug 2009 (data cut-off Dec 31 2008). The DSMC recommended release of the results to the Trial Committee for publication. The median follow-up is 6.0 years and 320 patients have died (175 ADT and 145 ADT+RT). 10% of patients had no follow-up data beyond 2006. The addition of RT to ADT significantly reduced the risk of death (hazard ratio [HR] 0.77, 95% CI 0.61-0.98, p=0.033). 140 patients died of disease and/or treatment (89 on ADT and 51 on ADT+RT) The disease specific survival HR was 0.57 (95% CI 0.41-0.81, p=0.001) favoring ADT+RT. The 10 year cumulative disease specific death rates were estimated at 15% with ADT+ RT and 23% with ADT alone. Grade ≥2 late GI toxicity rates were similar in both arms (proctitis, 1.3% ADT alone, 1.8% ADT+RT). Conclusions: The trial results indicate a substantial overall survival and disease specific survival benefit for the combined modality approach (ADT+RT) in the management of patients with locally advanced prostate cancer with no significant increase in late treatment toxicity. In view of this data combined modality therapy (ADT+RT) should be the standard treatment approach for these patients. Supported by NCI-US Grant #5U10CA077202-12, CCSRI Grant #15469. No significant financial relationships to disclose.

Current status of radiation therapy for bladder cancer

The role of radiation therapy in the management of muscle-invasive bladder cancer has evolved tremendously over the past several decades. Early on, radiation therapy alone was utilized as the preferred method of bladder preservation. Unfortunately, the results with this approach have been suboptimal. More recently, several protocols have been developed using a combined modality approach with chemotherapy. This has opened the door once again to the concept of bladder conservation as a potentially equivalent approach to radical cystectomy. While it is unlikely that a randomized trial comparing radical cystectomy with bladder preservation and chemoradiotherapy will be performed, the latter treatment strategy is gaining more support among practitioners. In selected patients with muscle-invasive bladder cancer, bladder-preservation approaches can achieve high rates of complete response, acceptable disease control and excellent long-term bladder function. The key to success for such programs is the careful selection of patients with favorable clinical features and close monitoring of the treatment response during therapy. Aggressive transurethral resection of bladder tumor to debulk disease and early referral for cystectomy in nonresponding patients are also highly critical for a successful outcome.

Hodgkin's lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Hodgkin's lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up