Circulating immune cell populations related to primary breast cancer, surgical removal, and radiotherapy revealed by flow cytometry analysis.

BACKGROUND: Advanced breast cancer (BC) impact immune cells in the blood but whether such effects may reflect the presence of early BC and its therapeutic management remains elusive. METHODS: To address this question, we used multiparametric flow cytometry to analyze circulating leukocytes in patients with early BC (n = 13) at the time of diagnosis, after surgery, and after adjuvant radiotherapy, compared to healthy individuals. Data were analyzed using a minimally supervised approach based on FlowSOM algorithm and validated manually. RESULTS: At the time of diagnosis, BC patients have an increased frequency of CD117+CD11b+ granulocytes, which was significantly reduced after tumor removal. Adjuvant radiotherapy increased the frequency of CD45RO+ memory CD4+ T cells and CD4+ regulatory T cells. FlowSOM algorithm analysis revealed several unanticipated populations, including cells negative for all markers tested, CD11b+CD15low, CD3+CD4-CD8-, CD3+CD4+CD8+, and CD3+CD8+CD127+CD45RO+ cells, associated with BC or radiotherapy. CONCLUSIONS: This study revealed changes in blood leukocytes associated with primary BC, surgical removal, and adjuvant radiotherapy. Specifically, it identified increased levels of CD117+ granulocytes, memory, and regulatory CD4+ T cells as potential biomarkers of BC and radiotherapy, respectively. Importantly, the study demonstrates the value of unsupervised analysis of complex flow cytometry data to unravel new cell populations of potential clinical relevance.

Gamma Knife radiosurgery for glossopharyngeal neuralgia: A study of 21 patients with long-term follow-up.

Objective Glossopharyngeal neuralgia (GPN) is a very rare condition, affecting the patient's quality of life. We report our experience in drug-resistant, idiopathic GPN, treated with Gamma Knife radiosurgery (GKRS), in terms of safety and efficiency, on a very long-term basis. Methods The study was opened, self-controlled, non-comparative and bicentric (Marseille and Lausanne University Hospitals). Patients treated with GKRS between 2003 and 2015 (models C, 4C and Perfexion) were included. A single 4-mm isocentre was positioned in the cisternal portion of the glossopharyngeal nerve, with a targeting based both on magnetic resonance imaging (MRI) and computed tomography (CT). The mean maximal dose delivered was 81.4 ± 6.7 Gy (median = 85 Gy, range = 60-90 Gy at the 100% isodose line). Results Twenty-one patients (11 women, 10 men) benefited from 25 procedures. The mean follow-up period was 5.2 ± 3 years (range = 0.9-12.1 years). Seventeen (81%) were initially pain-free after GKRS. At three months, six months and one year after radiosurgery, the percentage of patients with good outcome (BNI classes I to IIIA) was 87.6%, 100% and 81.8%, respectively. Ten cases (58.8%) from the initial pain-free ones had a recurrence, after a mean period of 13.6 ± 10.4 months (range = 3.1-36.6 months). Only three patients (14.2%) had recurrences (two for each one of them) requiring further surgeries. Three patients underwent a second GKRS procedure; one case needed a third GKRS. The former procedures were performed at 7, 17, 19 and 30 months after the first one, respectively. Furthermore, two patients needed additional interventions. At last follow-up, 17 cases (80.9%) were still pain-free without medication. The actuarial pain relief without new surgery was 83%. A transient complication (paraesthesia of the edge of the tongue) was seen in one case (4.8%). Conclusion GKRS is a valuable, minimally invasive, surgical alternative for idiopathic GPN, with a very high short- and long-term efficacy and without permanent complications. A quality imaging, including T2 CISS/Fiesta MRI and bone CT acquisitions for good visualisation of the nerve and the other bony anatomic landmarks, is essential for targeting accuracy and successful therapy.

Radiotherapy with concurrent and adjuvant temozolomide in children with newly diagnosed diffuse intrinsic pontine glioma.

The purpose of this study is to evaluate the efficacy and toxicity of radiation therapy (RT) with concurrent temozolomide (TMZ) chemotherapy followed by adjuvant TMZ in children with diffuse intrinsic pontine glioma (DIPG). Newly diagnosed patients younger than 18 years with histologically proven DIPG were treated with focal radiotherapy to a dose of 54 Gy in 30 fractions along with concurrent daily TMZ (75 mg/m(2)/day). Four weeks after completing the initial RT-TMZ schedule, adjuvant TMZ (200 mg/m(2)/day, days 1-5) was given every 28 days up to six cycles. Responses/progressions were assessed by clinical and 2-monthly MRI follow-up studies. Between September 2005 and September 2009, 21 patients with newly diagnosed histologically confirmed DIPG were eligible for this study. Median age at diagnosis was 6.4 years (range 4-16 years). At last update in August 2010, 17 children have died, 1 child was alive with progressive disease and 3 with stable disease. Metastatic relapse was documented in the cerebral site in two patients and in spinal cord in two cases. The median time to progression was 7.5 months (range 28 days-14.5 months) and the median survival was 11.7 months (range 26 days-17.5 months). The 1-year PFS and the 1-year OS were 33 and 50%, respectively. Five patients presented radiological findings compatible with pseudoprogression during the treatment. Haematological toxicity (Grade III/IV thrombocytopenia and leucopenia) was the most commonly found and led to dose reductions of TMZ in 58% of the patients. TMZ with radiation therapy has not yielded any significant improvement in outcome of children with DIPG and is associated with higher toxicity compared with radiotherapy alone. Novel treatment modalities are needed to improve the outcome of these patients.

Gamma Knife, CyberKnife, TomoTherapy: gadgets or useful tools?

PURPOSE OF REVIEW: This review provides information and an update on stereotactic radiosurgery (SRS) equipment, with a focus on intracranial lesions and brain neoplasms. RECENT FINDINGS: Gamma Knife radiosurgery represents the gold standard for intracranial radiosurgery, using a dedicated equipment, and has recently evolved with a newly designed technology, Leksell Gamma Knife Perfexion. Linear accelerator-based radiosurgery is more recent, and originally based on existing systems, either adapted or dedicated to radiosurgery. Equipment incorporating specific technologies, such as the robotic CyberKnife system, has been developed. Novel concepts in radiation therapy delivery techniques, such as intensity-modulated radiotherapy, were also developed; their integration with computed tomography imaging and helical delivery has led to the TomoTherapy system. Recent data on the management of intracranial tumors with radiosurgery illustrate the trend toward a larger use and acceptance of this therapeutic modality. SUMMARY: SRS has become an important alternative treatment for a variety of lesions. Each radiosurgery system has its advantages and limitations. The 'perfect' and ubiquitous system does not exist. The choice of a radiosurgery system may vary with the strategy and needs of specific radiosurgery programs. No center can afford to acquire every technology, and strategic choices have to be made. Institutions with large neurosurgery and radiation oncology programs usually have more than one system, allowing optimization of the management of patients with a choice of open neurosurgery, radiosurgery, and radiotherapy. Given its minimally invasive nature and increasing clinical acceptance, SRS will continue to progress and offer new advances as a therapeutic tool in neurosurgery and radiotherapy.

Hypofractionated radiotherapy in the treatment of diffuse intrinsic pontine glioma in children: a single institution's experience.

We report herein our institutional experience in the treatment of diffuse intrinsic pontine glioma (DIPG) with a hypofractionated external-beam radiotherapy schedule. Between April 1996 and January 2004, 22 patients (age 2.9-12.5 years) with newly diagnosed DIPG were treated by hypofractionated radiation therapy delivering a total dose of 45 Gy in daily fractions of 3 Gy, given over 3 weeks. No other treatment was applied concomitantly. Fourteen of the 22 patients received the prescribed dose of 45 Gy in 15 fractions of 3 Gy, and 2 patients received a total dose of 60 and 45 Gy with a combination of two different beams (photons and neutrons). In five cases the daily fraction was modified to 2 Gy due to intolerance, and one patient died due to serious intracranial hypertension after two fractions of 3 Gy and one of 2 Gy. Among 22 children, 14 patients showed clinical improvement, usually starting in the second week of treatment. No grade 3 or 4 acute toxicity from radiotherapy was observed. No treatment interruption was needed. In six patients, steroids could be discontinued within 1 month after the end of radiotherapy. Median time to progression and median overall survival were 5.7 months and 7.6 months, respectively. External radiotherapy with a radical hypofractionated regimen is feasible and well tolerated in children with newly diagnosed DIPG. However, this regimen does not seem to change overall survival in this setting. It could represent a short-duration alternative to more protracted regimens.

Total body irradiation (TBI) in pediatric patients. A single-center experience after 30 years of low-dose rate irradiation.

PURPOSE: To retrospectively analyze patient characteristics, treatment, and treatment outcome of pediatric patients with hematologic diseases treated with total body irradiation (TBI) between 1978 and 2006. PATIENTS AND METHODS: 32 pediatric patients were referred to the Department of Radiation-Oncology at the University of Zurich for TBI. Records of regular follow-up of 28 patients were available for review. Patient characteristics as well as treatment outcome regarding local control and overall survival were assessed. A total of 18 patients suffered from acute lymphoblastic leukemia (ALL), 5 from acute and 2 from chronic myelogenous leukemia, 1 from non-Hodgkin lymphoma, and 2 from anaplastic anemia. The cohort consisted of 15 patients referred after first remission and 13 patients with relapsed leukemia. Mean follow-up was 34 months (2-196 months) with 15 patients alive at the time of last follow-up. Eight patients died of recurrent disease, 1 of graft vs. host reaction, 2 of sepsis, and 2 patients died of a secondary malignancy. RESULTS: The 5-year overall survival rate (OS) was 60%. Overall survival was significantly inferior in patients treated after relapse compared to those treated for newly diagnosed leukemia (24% versus 74%; p=0.004). At the time of last follow-up, 11 patients survived for more than 36 months following TBI. Late effects (RTOG ≥ 3) were pneumonitis in 1 patient, chronic bronchitis in 1 patient, cardiomyopathy in 2 patients, severe cataractogenesis in 1 patient (48 months after TBI with 10 Gy in a single dose) and secondary malignancies in 2 patients (36 and 190 months after TBI). Growth disturbances were observed in all patients treated prepubertally. In 2 patients with identical twins treated at ages 2 and 7, a loss of 8% in final height of the treated twin was observed. CONCLUSION: As severe late sequelae after TBI, we observed 2 secondary malignancies in 11 patients who survived in excess of 36 months. However, long-term morbidity is moderate following treatment with the fractionated TBI at the low-dose rate that was generally used here. Conditioning for bone marrow transplantation without radiation is an attractive option, but is not sufficiently effective to completely replace TBI for the most common pediatric indications.

A phase I-II study to determine the maximum tolerated infusion rate of rituximab with special emphasis on monitoring the effect of rituximab on cardiac function.

PURPOSE: This phase I infusion rate escalation trial was undertaken to evaluate the maximum applicable infusion rate for rituximab without steroid premedication in patients having received one previous rituximab infusion. EXPERIMENTAL DESIGN: Cohorts of at least three patients were assigned to rituximab with or without concomitant chemotherapy. The initial infusion rate was 200 mg/h in the first cohort, and was increased by 100 mg/h in each subsequent cohort to a maximum of 700 mg/h. In each patient the infusion rate was increased by 100 mg/h every 30 minutes to the total dose (375 mg/m2). In the first six cohorts (21 patients), two well-tolerated rituximab administrations were required; in the 7th cohort (11 patients) one previously well-tolerated rituximab infusion was required. Patients did not receive steroid premedication and were monitored with electrocardiograms (ECG), echocardiograms, Holter ECGs, troponin, and brain natriuretic peptide (BNP). RESULTS: Thirty-two patients were included and 128 cycles were done, 85 at a rate of 700 mg/h. Patients tolerated infusion rates without major side effects. There were no new clinically relevant ECG alterations. Troponin (< 0.1 ng/L) and mean cardiac ejection fraction (65%) remained in the reference range; BNP baseline level increased significantly 24 hours after rituximab administration (from 30.4 to 64.1 ng/L; P < 0.0001). CONCLUSIONS: Rituximab can be administered safely at 700 mg/h without steroid premedication in patients having received at least one rituximab dose in the previous 3 months.

Radiosurgery in the management of brain metastasis: a retrospective single-center study comparing Gamma Knife and LINAC treatment.

OBJECTIVE The authors present a retrospective analysis of a single-center experience with treatment of brain metastases using Gamma Knife (GK) and linear accelerator (LINAC)-based radiosurgery and compare the results. METHODS From July 2010 to July 2012, 63 patients with brain metastases were treated with radiosurgery. Among them, 28 (with 83 lesions) were treated with a GK unit and 35 (with 47 lesions) with a LINAC. The primary outcome was local progression-free survival (LPFS), evaluated on a per-lesion basis. The secondary outcome was overall survival (OS), evaluated per patient. Statistical analysis included standard tests and Cox regression with shared-frailty models to account for the within-patient correlation. RESULTS The mean follow-up period was 11.7 months (median 7.9 months, range 1.7-32 months) for GK and 18.1 months (median 17 months, range 7.5-28.7 months) for LINAC. The median number of lesions per patient was 2.5 (range 1-9) in the GK group and 1 (range 1-3) in the LINAC group (p < 0.01, 2-sample t-test). There were more radioresistant lesions (e.g., melanoma) and more lesions located in functional areas in the GK group. Additional technical reasons for choosing GK instead of LINAC were limitations of LINAC movements, especially if lesions were located in the lower posterior fossa or multiple lesions were close to highly functional areas (e.g., the brainstem), precluding optimal dosimetry with LINAC. The median marginal dose was 24 Gy with GK and 20 Gy with LINAC (p < 0.01, 2-sample t-test). For GK, the actuarial LPFS rate at 3, 6, 9, 12, and 17 months was 96.96%, 96.96%, 96.96%, 88.1%, and 81.5%, remaining stable until 32 months. For LINAC the rate at 3, 6, 12, 17, 24, and 33 months was 91.5%, 91.5%, 91.5%, 79.9%, 55.5%, and 17.1% (log-rank p = 0.03). In the Cox regression with shared-frailty model, the risk of local progression in the LINAC group was almost twice that of the GK group (HR 1.92, p > 0.05). The mean OS was 16.0 months (95% CI 11.2-20.9 months) in the GK group, compared with 20.9 months (95% CI 16.4-25.3 months) in the LINAC group. Univariate and multivariate analysis showed that a lower graded prognostic assessment (GPA) score, noncontrolled systemic status at last radiological assessment, and older age were associated with lower OS; after adjustment of these covariables by Cox regression, the OS was similar in the 2 groups. CONCLUSIONS In this retrospective study comparing GK and LINAC-based radiosurgery for brain metastases, patients with more severe disease were treated by GK, including those harboring lesions of greater number, of radioresistant type, or in highly functional areas. The risk of local progression for the LINAC group was almost twice that in the GK group, although the difference was not statistically significant. Importantly, the OS rates were similar for the 2 groups, although GK was used in patients with more complex brain metastatic disease and with no other therapeutic alternative.

Treatment outcome and prognostic factors for adult patients with medulloblastoma: The Rare Cancer Network (RCN) experience.

BACKGROUND AND PURPOSE: The optimal treatment for adults with newly diagnosed medulloblastoma (MB) has not been defined. We report a large series of cases from the Rare Cancer Network. MATERIAL AND METHODS: Thirteen institutions enrolled 206 MB patients who underwent postoperative radiotherapy (RT) between 1976 and 2014. Log-rank univariate and Cox-modeled multivariate analyses were used to analyze data collected. RESULTS: Median patient age was 29 years; follow-up was 31 months. All patients had the tumor resected; surgery was complete in 140 (68%) patients. Postoperative RT was given in 202 (98%) patients, and 94% received craniospinal irradiation (CSI) and, usually, a posterior fossa boost. Ninety-eight (48%) patients had chemotherapy, mostly cisplatin and vincristine-based. The 10-year local control, overall survival, and disease-free survival rates were 46%, 51%, and 38%, respectively. In multivariate analyses, Karnofsky Performance Status (KPS) ≥80 and CSI were significant for disease-free and overall survival (P ≤ .04 for all); receiving chemotherapy and KPS ≥80 correlated with better local-control rates. CONCLUSIONS: Patients with high KPS who received CSI had better rates of disease-free and overall survival. Chemotherapy was associated with better local control. These results may serve as a benchmark for future studies designed to improve outcomes for adults with medulloblastoma.

Clinical and biochemical responses after Gamma Knife surgery for a dopamine-secreting paraganglioma: case report.

INTRODUCTION: The efficacy of Gamma Knife surgery (GKS) in local tumor control of non-secreting paragangliomas (PGLs) has been fully described by previous studies. However, with regard to secreting PGL, only one previous case report exists advocating its efficacy at a biological level. CASE REPORT: The aims of this study were: 1) to evaluate the safety/efficacy of GKS in a dopamine-secreting PGL; 2) to investigate whether the biological concentrations of free methoxytyramine could be used as a marker of treatment efficacy during the follow-up. We describe the case of a 62-year-old man diagnosed with left PGL. He initially underwent complete surgical excision. Thirty months after, he developed recurrent biological and neuroradiological disease; the most sensitive biomarker for monitoring the disease, concentration of plasma free methoxytyramine, started to increase. GKS was performed at a maximal marginal dose of 16 Gy. During the following 30 months, concentration of free methoxytyramine gradually decreased from 0.14 nmol/l (2*URL) before GKS to 0.09 nmol/l, 6 months after GKS and 0.07 nmol/l at the last follow-up after GKS (1.1*URL), confirming the efficacy of the treatment. Additionally, at 30 months there was approximately 36.6% shrinkage from the initial target volume. CONCLUSION: The GKS treatment was safe and effective, this being confirmed clinically, neuroradiologically and biologically. The case illustrates the importance of laboratory tests taking into account methoxytyramine when analyzing biological samples to assess the biochemical activity of a PGL. In addition, the identification of methoxytyramine as a unique positive biomarker could designate it for the monitoring of tumor relapse after treatments, including Gamma Knife surgery.

PET Imaging in Glioma: The Neuro-Oncologist's Expectations.

PET-imaging is a useful tool for management of certain glioma patients. The variable availability of adequate tracers, their short half-life, but also administrative obstacles and financial constraints are hampering the prospective evaluation of PET. Its impact in tumor localization and accurate diagnosis, in treatment response evaluation and ultimately patient outcome needs to be demonstrated. Systematic algorithms for optimal and economical use are needed. We summarize the limitations of the usual imaging techniques, and of the added value of PET-imaging in specific clinical situations. We call for prospective studies and registries rather than the current largely resource-driven use of this valuable technique.

Fractionated stereotactic radiotherapy with static field conformal and non coplanar arcs for pediatric patients with craniopharyngioma: analysis of long term visual outcome and endocrine toxicity.

We assessed the efficacy and the toxicity for pediatric craniopharyngioma patients of fractionated stereotactic radiotherapy (FSRT). Between May 2000 and May 2009, 9 patients (male to female ratio, 5:4) with craniopharyngiomas underwent FSRT (median dose, 54 Gy). Among the 9 patients, 6 received radiation therapy (RT) for recurrent tumors and 3 for residual disease as adjuvant therapy after incomplete surgery. Median tumor volume was 2.3 cm3 (range, 0.1-5.8). The median target coverage was 93.7% (range 79.3-99.8%). The median conformity index was 0.94 (range, 0.6-1.4). Dose to the hippocampal region was assessed for all patients.After a median follow-up of 62.5 months (range, 32-127)the treated volume decreased in size in four of eight patients (50%). One patient was lost to follow-up. Local control and survival rates at 3 years were 100% and there were no marginal relapses. One patient, with a chronic bilateral papillary oedema after surgery, visual defect deteriorated after FSRT to a complete hemianopsia. One male patient with normal pituitary function before FSRT presented with precocious puberty at the age of 7.4 years, 24 months after FSRT. Four patients (50%) were severely obese at their last visit. FSRT is a safe treatment option for craniopharyngioma after incomplete resection.

Pseudoprogression after high-dose busulfan-thiotepa with autologous stem cell transplantation and radiation therapy in children with brain tumors: Impact on survival.

Children with a brain tumor treated with high-dose busulfan-thiotepa with autologous stem cell transplantation (ASCT) and radiation therapy (RT) often experience radiographic changes during follow-up. The purpose of the study was to identify the incidence, time course, risk factors, and clinical outcome of this complication. From May 1988 through May 2007, 110 patients (median age, 3.6 years; range, 1 month to 15.3 years) with a brain tumor had received 1 course of high-dose busulfan-thiotepa with stem cell rescue, followed or preceded by RT as part of their treatment. All MRI follow-up examinations were systematically reviewed. Twenty-three patients (21%) developed neuroradiological abnormalities at a median time of 9.2 months (range, 5.6-17.3 months) after ASCT. All contrast-enhancing lesions appeared in patients who had received RT after ASCT and were localized inside the 50-55Gy isodoses. They disappeared in 14 of 23 patients after a median time of 8 months (range, 3-17 months), leaving microcalcifications in some cases. The presence of MRI abnormalities was an independent prognostic factor for overall survival in the multivariate analysis (hazard ratio, 0.12; 95% confidence interval [CI], 0.04-0.33), with a 5-year overall survival rate of 84% among patients with MRI abnormalities (95% CI, 62-94), compared with 27% (95% CI, 19-37) among those without lesions. MRI-detectable pseudoprogression is a common early finding in children treated with high-dose busulfan-thiotepa followed by radiation therapy and is correlated with a better outcome.

IMRT or conformal radiotherapy for adjuvant treatment of retroperitoneal sarcoma?

PURPOSE: To compare the dose distribution between three-dimensional conformal radiotherapy (3DCRT), intensity modulated radiotherapy (IMRT) with six coplanar beams (6b-IMRT) and IMRT with nine coplanar beams (9b-IMRT) during adjuvant radiotherapy for retroperitoneal sarcoma. METHODS AND MATERIALS: The 10 most recent patients who had received adjuvant radiotherapy were reviewed. Three different treatment plans were generated (3DCRT, 6b-IMRT and 9b-IMRT) to deliver 50.4 Gy in 28 fractions. The dose delivered to the organs at risk (intestinal cavity (IC), contra- and ipsilateral kidney, liver, stomach and whole body), and the conformity index (CI) were compared. RESULTS: The integral dose to the intestinal cavity was similar with the three modalities but the dose distribution was different, with a change-over around 25 Gy: the V50 and the V40 were reduced five- and twofold, respectively, with IMRT compared to 3DCRT, and the V20 was increased by about 25% with IMRT. A similar integral dose was delivered to the whole body with the three modalities. The treated volume (V95 body) was approximately halved with IMRT compared to 3DCRT, and the CI was twice as good with IMRT than with 3DCRT. As expected, the V5 (body) was higher with IMRT compared to 3DCRT (p<0.0001) (a 12% increase with 6b-IMRT and a 21% increase with 9b-IMRT). Compared to 3DCRT, the mean dose delivered to the contralateral kidney increased from 1.5 to 4-4.4 Gy with IMRT. The number of monitor units was increased with IMRT, especially when nine beams were used instead of six. CONCLUSIONS: As expected, IMRT greatly reduced the high-dose irradiated volume and increased the low-dose exposure of the intestinal cavity, with a change-over around 25 Gy, compared to 3DCRT. The conformity index was compellingly better with IMRT. The integral dose delivered to the whole body was conserved with both 3DCRT and IMRT. Longer follow-up is needed to assess late toxicities to the small bowel, contralateral kidney and the risk of second cancers.

Adenine phosphoribosyltransferase (APRT) deficiency: a new genetic mutation with early recurrent renal stone disease in kidney transplantation.

Adenine phosphoribosyltransferase (APRT) deficiency, a rare inborn error inherited as an autosomic recessive trait, presents with 2,8-dihydroxyadenine (2,8-DHA) crystal nephropathy. We describe clinical, biochemical and molecular findings in a renal transplant recipient with renal failure, 2,8-DHA stones and no measurable erythrocyte APRT activity. Homozygous C > G substitution at -3 in the splicing site of exon 2 (IVS2 -3 c > g) was found in the APRT gene. The patient's asymptomatic brother was heterozygous for such mutation, and his APRT activity was 23% of controls. A splicing alteration leading to incorrect gene transcription and virtually absent APRT activity is seemingly associated with the newly identified mutation.

Consolidative involved field radiotherapy after high dose chemotherapy and autologous stem cell transplantation for non-Hodgkin's lymphoma: a case-control study.

The role of involved field radiation therapy (IF-RT) after high dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) for non-Hodgkin's lymphoma (NHL) has not been conclusively defined. It has been hypothesized that HDC might obviate the need of consolidative IF-RT. A retrospective matched-pair analysis of patients undergoing HDC and ASCT with or without consolidative IF-RT has been performed. Fifteen patients treated with IF-RT after ASCT were compared with 15 patients without IF-RT, identical for histology, stage and treatment response to HDC/ASCT as well as comparable for international prognostic index (IPI) score, age and gender. After a mean follow-up time of 65 +/- 45 months, none of the patients with consolidative IF-RT following HDC and ASCT relapsed within the involved field compared to six patients without consolidative IF-RT (IF-failure risk at 5 years: 0% vs. 40%; p < 0.005). In most of the cases, local relapse was seen in patients with bulky disease. The 5-year risk for loco-regional failure was 7% after consolidative IF-RT and 38% in patients without IF-RT (p = 0.02) while the 5-year risk for developing distant recurrences was similar in both groups (30% with IF-RT vs. 35% non-IF-RT; p = 0.7). Overall survival at 5 years was similar with 79% (IF-RT) and 65% (non-IF-RT), respectively (p = 0.2). Acute toxicity due to consolidative IF-RT was mild in most cases and severe acute toxicity was noticed in only one patient (7%). Long-term toxicities observed after IF-RT were coronary artery disease, secondary malignancy unrelated to the RT-field, angina abdominalis, hypothyroidism and teeth decay. Recurrence of NHL at sites of macroscopic disease remains common despite HDC. IF-RT achieves excellent local regional control and consolidative IF-RT after ASCT seems indicated, particularly in patients with bulky disease. In the absence of a prospective randomized trial and proven impact on survival rates, IF-RT can be recommended as an option post-ASCT to enhance local disease control.

HIV-specific differences in outcome of squamous cell carcinoma of the anal canal: a multicentric cohort study of HIV-positive patients receiving highly active antiretroviral therapy.

PURPOSE: To define clinical outcome after definitive chemoradiotherapy (CRT) of anal carcinoma in HIV-infected patients treated with highly active antiretroviral therapy (HAART). PATIENTS AND METHODS: A multicentric cohort comparison of 40 HIV-positive patients with HAART and 81 HIV-negative patients treated with radiotherapy (RT) or CRT was retrospectively performed. Local disease control (LC), relapse-free survival (RFS), overall survival (OS), cancer-specific survival (CSS), toxicity, and prognostic factors were investigated. RESULTS: HIV-positive patients were younger (mean age, 48 v 62 years; P < .0005), predominantly male (93% v 25%; P < .0005), and with early-stage (P = .06) and large-cell histology (90% v 67%; P = .005) disease. RT or CRT resulted in complete response in 92% (HIV positive) and 96% (HIV negative) of cases. Five-year OS was 61% (95% CI, 44% to 78%) in HIV-positive and 65% (95% CI, 53% to 77%) in HIV-negative patients (median follow-up, 36 months). Five-year LC was 38% (95% CI, 5% to 71%) in HIV-positive and 87% (95% CI, 79% to 95%) in HIV-negative patients (P = .008) compromising CSS and sphincter preservation. Grade 3/4 acute skin (35% v 17% [HIV negative]; P = .04) and hematologic (33% v 12% [HIV negative]; P = .08) toxicity together approximated 50% in HIV-positive patients. RFS in HIV-positive patients was associated with RT dose (P = .08) and severe acute skin toxicity (P = .04). CONCLUSION: Long-term LC and acute toxicity represent major clinical challenges in HIV-positive patients with anal carcinoma. Even if fluoropyrimidine-based CRT is feasible and may result in similar response rates and OS as in HIV-negative patients, improved treatment strategies with better long-term outcome are warranted.