Proton therapy of iris melanoma with 50 CGE

Purpose

The aim of this study was to evaluate local tumour control, incidence of radiation-induced glaucoma and associated interventions of sector-based and whole anterior segment proton beam therapy (PBT) for the treatment of iris melanoma.

Patients and methods

We retrospectively analysed the data of 77 patients with iris melanoma who underwent PBT applied as 50 CGE in four daily fractions. Of the patients, 47 received PBT with a circular-shaped collimator and 30 with a conformal sector-shaped target volume. Local control, eye preservation and secondary glaucoma were evaluated.

Results

Median follow-up time was 54.9 months. Local tumour control was 100% in patients receiving whole anterior segment irradiation. Two patients developed pigment dispersion in the non-irradiated area after sector-based PBT and received whole anterior segment salvage PBT. The mean volume of ciliary body irradiated was 89.0% and 34.9% for whole anterior segment and lesion-based irradiation, respectively. At the end of follow-up, secondary glaucoma was found in 74.3% of the patients with whole anterior segment irradiation and in 19.2% with sector-based irradiation. Patients with sector-based PBT had a stable visual acuity of logMAR 0.1, while it declined from logMAR 0.1 to 0.4 after whole anterior segment irradiation.

Conclusion

We found a significant reduction in radiation-induced secondary glaucoma and glaucoma-associated surgical interventions and stable visual acuity after sector-based irradiation compared with whole anterior segment irradiation. Sector-based irradiation revealed a higher risk for local recurrence, but selected patients with well-circumscribed iris melanoma benefit from applying a lesion-based target volume when treated with sector-based PBT.

     

Heart irradiation reduces microvascular density and accumulation of HSPA1 in mice

Purpose

Improvement of radiotherapy techniques reduces the exposure of normal tissues to ionizing radiation. However, the risk of radiation-related late effects remains elevated. In the present study, we investigated long-term effects of radiation on heart muscle morphology.

Materials and methods

We established a mouse model to study microvascular density (MVD), deposition of collagen fibers, and changes in accumulation of heat shock 70?kDa protein 1 (HSPA1) in irradiated heart tissue. Hearts of C57BL/6 mice received a single dose of X?ray radiation in the range 0.2–16?Gy. Analyses were performed 20, 40, and 60 weeks after irradiation.

Results

Reduction in MD was revealed as a long-term effect observed 20–60 weeks after irradiation. Moreover, a significant and dose-dependent increase in accumulation of HSPA1, both cytoplasmic and nuclear, was observed in heart tissues collected 20 weeks after irradiation. We also noticed an increase in collagen deposition in hearts treated with higher doses.

Conclusions

This study shows that some changes induced by radiation in the heart tissue, such as reduction in microvessel density, increase in collagen deposition, and accumulation of HSPA1, are observed as long-term effects which might be associated with late radiation cardiotoxicity.

     

Simulation study of dosimetric effect in proton beam therapy using concomitant boost technique for unresectable pancreatic cancers

Purpose

The purpose of this study is to investigate the dose distribution of proton beam therapy (PBT) using a concomitant boost technique for unresectable pancreatic cancers.

Materials and methods

This simulation study involved 36 patients with unresectable pancreatic cancer. The irradiation dose was set as 67.5 gray equivalent (GyE) with 25 fractions using concomitant boost technique. The irradiation dose was set as 50 GyE to cover the whole target and another posterior beam of 17.5 GyE was added to ensure that 10% isodose line was not delivered to the gastrointestinal (GI) tract. Dose distribution of the gross tumor volume and GI tract was examined.

Results

V_{55GyE, 60GyE, 65GyE} were 80.8, 66.5, and 42.4%, respectively, and mean dose was 64.1 GyE in all patients. The distance from the GI tract showed significant difference in dose distribution (P?=?0.002 in V_55GyE, 0.0009 in V_60GyE, 0.003 in V_65GyE, and 0.02 in mean dose, respectively). Location, tumor diameter, or lymph nodes metastasis did not show any difference.

Conclusions

We found that irradiated dose is closely related to the distance from the GI tract. Clinically, this protocol is expected to have outstanding effects on local control of tumors compared to conventional PBT.

     

A clinical example of extreme dose exposure for an implanted cardioverter–defibrillator

Introduction

Considering that the number of malignant diseases in patients over 65 years of age is increasing, it often occurs that patients who carry a cardiac implanted electronic device must undergo radiotherapy. Ionizing radiation can disturb the function of the implantable cardioverter–defibrillator (ICD). As a result of this, an update of the DEGRO/DKG guidelines for radiotherapy of this patient group has been published.

Methods

We report the case of a patient with an ICD and T?lymphoblastic lymphoma with cardiac involvement, who received i.a. a total body irradiation with 8?Gy followed by a consolidating radiotherapy of the pericardium with 14?Gy as well as additional radiotherapy courses after consecutive recurrences. For the purposes of the treatment, the antitachyarrhythmia (ATA) therapy was deactivated and temporarily replaced through a life vest.

Results

According to the current DEGRO guidelines for irradiation of patients with cardiac implanted electronic devices, a categorization of the patient in the “high-risk” group was made. Furthermore, regular telemetric checks of the ICD device were performed before and after treatment. Despite unavailable declaration of the manufacturer regarding the cumulative tolerable dose and DEGRO recommendation for a cumulative dose <2?Gy, the aftercare was unproblematic and normal values were assessed for all relevant ICD parameters, despite a cumulative dose >10?Gy in the device.

Conclusion

This case shows that if the cardiac implanted electronic devices are not directly irradiated und the energy used is reduced to 6 MV, irradiation-induced damage is less likely and can possibly be prevented.

     

Protective effects of systemic dermatan sulfate treatment in a preclinical model of radiation-induced oral mucositis

Purpose

Oral mucositis is a frequent, dose-limiting side effect of radio(chemo)therapy of head-and-neck malignancies. The epithelial radiation response is based on multiple tissue changes, which could offer targets for a biologically tailored treatment. The potential of dermatan sulfate (DS) to modulate radiation-induced oral mucositis was tested in an established preclinical mucositis model.

Methods

Irradiation was either applied alone or in combination with daily DS treatment (4?mg/kg, subcutaneously) over varying time intervals. Irradiation comprised single dose irradiation with graded doses to the lower tongue surface or daily fractionated irradiation of the whole tongue. Fractionation protocols (5?×?3?Gy/week) over one (days 0–4) or two weeks (days 0–4, 7–11) were terminated by an additional local single dose irradiation to a defined treatment field on the lower tongue surface to induce the mucosal radiation response. The additional single dose irradiation (top-up) on day 7 (after one week of fractionation) or day 14 (after 2 weeks of fractionation) comprised graded doses in order to generate full dose–effect curves. Ulceration of the epithelium of the lower tongue, corresponding to confluent mucositis, was analysed as clinically relevant endpoint. Additionally, the time course parameters, latent time and ulcer duration were analysed.

Results

DS treatment significantly reduced the incidence of ulcerations. DS application over longer time intervals resulted in a more pronounced reduction of ulcer frequency, increased latent times and reduced ulcer duration.

Conclusion

DS has a significant mucositis-ameliorating activity with pronounced effects on mucositis frequency as well as on time course parameters.

     

Systemic administration of heparin ameliorates radiation-induced oral mucositis—preclinical studies in mice

Purpose

The present study investigates the impact of systemic application of heparins on the manifestation of radiation-induced oral mucositis in a well-established mouse model.

Materials and methods

Male C3H/Neu mice were irradiated with either single-dose or fractionated irradiation protocols with 5?×?3 Gy/week, given over one (days 0–4) or two (days 0–4, 7–11) weeks. All fractionation protocols were concluded by a local test irradiation (day 7/14) using graded doses to generate complete dose–effect curves. Daily doses of unfractionated or low molecular weight heparin (40 or 200 I.U./mouse, respectively) were applied subcutaneously over varying time intervals. The incidence and the time course of mucosal ulceration, corresponding to confluent mucositis in patients (RTOG/EORTC grade 3), were analysed as clinically relevant endpoints.

Results

Systemic application of heparins significantly increased the iso-effective doses for the induction of mucosal ulceration, particularly in combination with fractionated irradiation protocols. Moreover, a tentative prolongation of the latent time and a pronounced reduction of the ulcer duration were observed.

Conclusion

These data provide the first evidence for a protective and/or mitigative effect of heparins for radiation-induced oral mucositis. Further studies are ongoing investigating the underlying mechanism.

     

Beurteilung von fraglichen Geschwister- bzw. Halbgeschwisterfällen

Background

The freely available software FamLinkX allows for the statistical calculation of closely linked X?chromosomal STR markers in cases of complex kinship.

Aim of the study

The study presents preliminary results for the pairwise comparison of persons with alleged full or half siblings. Multiple calculations show the influence of observed and expected haplotype frequencies.

Materials and methods

Data obtained using the Argus X12-Kit (from a haplotype frequency database of 1,037 Germans) and with commonly used autosomal STR markers in cases of kinship analysis were evaluated. Additionally, unrelated people with matching possibilities in their haplotypes were compared. The calculation of the likelihood ratios was performed under the presumption of different weights for observed and expected haplotype frequencies.

Results

The likelihood ratios for the assumed full or half siblings vary greatly depending on the sex and on the number of shared X?chromosomal haplotypes.

Discussion

FamLinkX is a tool that is capable of dealing with not only linkage and linkage disequilibrium, but also rare mutations and recombinations. The differential weights of rare haplotype frequencies have a profound impact on results. The differentiation between random matches when comparing two unrelated persons in contrast to common inherited traits in maternal half-siblings remains difficult and requires additional testing.

     

Upregulated epithelial junction expression represents a novel parameter of the epithelial radiation response to fractionated irradiation in oral mucosa

Purpose

During head and neck cancer treatment, the radiation response of the oral mucosa represents a frequent early side effect. Besides radiation-induced inhibition of proliferation, various other cellular responses occur. The radiation response of adherens and tight junction proteins was so far mostly investigated with large single-dose irradiation protocols, in vivo and in vitro. Therefore, the current study was initiated to investigate the impact of daily fractionated irradiation on the expression of adherens and tight junction proteins in vivo.

Materials and methods

Fractionation with 5?×?3?Gy/week (days 0–4, 7–11) was given to the snouts of mice. Groups of 5 animals per day were euthanized every second day between day 0 (unirradiated controls) and day 14, and their tongues subjected to histological processing. Adherens junction marker (β-catenin and E?cadherin) and tight junction marker (claudin-1 and occludin) expression was analysed in the oral mucosa of unirradiated controls and during two weeks of fractionated irradiation.

Results

Adherens as well as tight junction marker proteins were rapidly and consistently upregulated in both the germinal as well as the functional layer of the oral mucosa. This represents a previously unknown parameter of the epithelial radiation response to clinically relevant fractionation protocols.

Conclusion

Fractionated irradiation significantly enhanced the expression of all proteins investigated. This study revealed a new parameter of the epithelial radiation response to fractionated irradiation.

     

Individualization of post-mastectomy radiotherapy and regional nodal irradiation based on treatment response after neoadjuvant chemotherapy for breast cancer

Purpose

To review the evidence regarding post-mastectomy radiotherapy (PMRT) and regional nodal irradiation (RNI) after neoadjuvant chemotherapy (NACT) for breast cancer, with a special focus on individualization of adjuvant radiotherapy based on treatment response.

Methods

A systematic literature search using the PubMed/Medline database was performed. We included prospective and retrospective reports with a minimum of 10 patients that had been published since 1^st January 2000, and provided clinical outcome data analyzed by treatment response and radiotherapy.

Results

Out of 763 articles identified via PubMed/Medline and hand search, 68 full text-articles were assessed for eligibility after screening of title and abstract. 13 studies were included in the systematic review, 9 for PMRT and 5 for RNI. All included studies were retrospective reports.

Conclusions

There is a considerable lack of evidence regarding the role of adjuvant radiotherapy and its individualization based on treatment response after NACT. Results of prospective randomized trials such as NSABP B?51/RTOG 1304 and Alliance A11202 are eagerly awaited.

     

Medulloblastoma in adults

Purpose

Adult medulloblastoma is a rare disease treated according to the current pediatric treatment guidelines. This retrospective analysis investigated the clinical outcomes and prognostic factors of adult medulloblastoma patients, who received multimodal therapy at our institution.

Methods

Treatment charts of all patients over the age of 15 years of age with de novo medulloblastoma, who had been treated at our institution between 2001 and 2014, were retrospectively analyzed. Patients’ demographic parameters, initial symptoms, treatment modalities, toxicities, and survival outcomes were investigated.

Results

In all, 21 patients with a median age of 30.2 years were identified. The most frequent histologies were desmoplastic and classic, and the most common molecular subtype was sonic hedgehog (SHH). After tumor resection, all patients received craniospinal irradiation (median dose 35.2?Gy) and a boost to the posterior fossa (median dose 19.8?Gy). Simultaneous chemotherapy with vincristine was given to 20 patients and sequential chemotherapy to 15 patients. The most common side effects were hematological toxicities. Median overall survival (OS) has not been reached after a median follow-up of 92 months. Estimated 5? and 10-year OS was 89 and 80%, respectively. Estimated 5? and 10-year progression-free survival (PFS) was 89 and 81%, respectively. In univariate analysis, a shorter interval between tumor resection and end of irradiation was significantly associated with improved OS and PFS, anaplastic histology with worse OS and PFS.

Conclusions

The combined modality treatment showed a good outcome in adults with medulloblastoma. Treatment time was revealed to be prognostic and should be kept as short as possible.

     

Stereotactic radiotherapy for choroidal melanomas by means of HybridArc™

Purpose

Stereotactic radiotherapy (SRT) is suitable to treat ocular tumours. The optimal beam geometry for SRT, however, has not been defined. Here we evaluate a combination technique with dynamic conformal arcs (DCAs) and intensity-modulated static fields (IMRT), known as HybridArc? (HA).

Methods

For the first consecutive 25 cases with choroidal melanomas with volumes of 0.02 to 1.18?cm³ treated with 50?Gy in five fractions, the results with respect to dose conformity, homogeneity, and dose distributions were summarised. To describe the dose distribution at the planning target volume (PTV) boundary, we defined a spatially averaged dose gradient (SADG) and compared it with Paddick’s gradient index (GI). We made dosimetric comparisons between HA and other irradiation techniques.

Results

The PTVs ranged from 0.42 to 3.37?cm³. The conformity index (CI) was 1.25?±?0.15, and the homogeneity index (HI) 0.08?±?0.02. The SADG was (?3.5?±?0.5) Gy/mm or (?7.0?±?1.0) %/mm between the isodose levels 95 and 20%; local minima reached ?11.5?Gy/mm or ?22.9%/mm. The coefficient of determination for a nonlinear regression of GI on SADG was 0.072. After a median follow-up time of 19.6 months, local tumour control was 100% without any case of post-therapeutic enucleation. Two patients (8%) developed liver metastases.

Conclusion

SRT of ocular tumours by HA is highly appropriate, and HA is superior to intensity-modulated arc therapy (IMAT) concerning dose reduction in organs at risk (OARs). The novel gradient measure SADG is more informative than Paddick’s GI.

     

Does selective pleural irradiation of malignant pleural mesothelioma allow radiation dose escalation?

Background

After lung-sparing radiotherapy for malignant pleural mesothelioma (MPM), local failure at sites of previous gross disease represents the dominant form of failure. Our aim is to investigate if selective irradiation of the gross pleural disease only can allow dose escalation.

Materials and methods

In all, 12 consecutive stage I–IV MPM patients (6 left-sided and 6 right-sided) were retrospectively identified and included. A magnetic resonance imaging-based pleural gross tumor volume (GTV) was contoured. Two sets of planning target volumes (PTV) were generated for each patient: (1) a “selective” PTV (S-PTV), originating from a 5-mm isotropic expansion from the GTV and (2) an “elective” PTV (E-PTV), originating from a 5-mm isotropic expansion from the whole ipsilateral pleural space. Two sets of volumetric modulated arc therapy (VMAT) treatment plans were generated: a “selective” pleural irradiation plan (SPI plan) and an “elective” pleural irradiation plan (EPI plan, planned with a simultaneous integrated boost technique [SIB]).

Results

In the SPI plans, the average median dose to the S?PTV was 53.6?Gy (range 41–63.6?Gy). In 4 of 12 patients, it was possible to escalate the dose to the S?PTV to >58?Gy. In the EPI plans, the average median doses to the E?PTV and to the S?PTV were 48.6?Gy (range 38.5–58.7) and 49?Gy (range 38.6–59.5?Gy), respectively. No significant dose escalation was achievable.

Conclusion

The omission of the elective irradiation of the whole ipsilateral pleural space allowed dose escalation from 49?Gy to more than 58?Gy in 4 of 12 chemonaive MPM patients. This strategy may form the basis for nonsurgical radical combined modality treatment of MPM.

     

Predictors for occlusion of cerebral AVMs following radiation therapy

Background

Intracranial arteriovenous malformations (AVMs) may show a harmful development. AVMs are treated by surgery, embolization, or radiation therapy.

Objective

This study investigated obliteration rates and side effects in patients with AVMs treated by radiation therapy.

Methods

A total of 40 cases treated between 2005 and 2013 were analyzed. Single-dose stereotactic radiosurgery (SRS) was received by 13 patients and 27 received hypofractionated stereotactic radiation therapy (HSRT). In 20 patients, endovascular embolization had been performed prior to irradiation and 24 patients (60?%) had a history of previous intracranial hemorrhage.

Results

Treatment resulted in complete obliteration (CO) in 23/40 cases and partial obliteration in 8/40. CO was achieved in 85?% of patients receiving SRS compared to 44?% of those receiving HSRT. In the HSRT group, a first indication of an influence of AVM volume on obliteration rate was found. Equivalent 2 Gy fraction doses (EQD2) >70 Gy showed an obliteration rate of 50?%. Prior embolization was significantly associated with a higher portion of CO (p = 0.032). Median latency period (24.2 vs. 26 months) until CO was similar in both groups (SRS vs. HSRT). The rate of intracranial hemorrhage in patients with no prior bleeding events was 0?%.

Conclusion

Excellent obliteration rates were achieved by SRS. Consistent with the literature, this data analysis suggests that the results of HSRT are volume-dependent. Furthermore, regimens with EQD2 doses >70 Gy appear more likely to achieve obliteration than schemes with lower doses. The findings indicate that radiation therapy does not increase the risk of bleeding. Prior embolization may have a good prognostic impact.

     

Radiotherapy of painful heel spur with two fractionation regimens

Background

In this randomized multicenter trial, we compared the effect of a lower single dose of 0.5?Gy vs. a standard single dose of 1?Gy concerning pain relief and quality of life, while maintaining a uniform total dose of 6?Gy. On the basis of laboratory observations, the lower single dose would be expected to be more effective.

Patients and methods

A total of 127 patients suffering from painful heel spur were randomized: Patients in the standard group were treated with single fractions of 6 × 1?Gy twice a week, while the experimental group was treated with single fractions of 12 × 0.5?Gy three times a week. Patients who did not show satisfactory pain relief after 12 weeks were offered re-irradiation with the standard dose. The study’s primary endpoints were pain relief and quality of life. Therapy results were evaluated and compared based on follow-up examinations after 12 and 48 weeks.

Results

The data of 117 patients could be evaluated. There was no significant difference between the groups concerning the results of a visual analogue scale (VAS), Calcaneodynia Score (CS), and the somatic scale of the 12-Item Short-Form Health Survey(SF-12). Patients undergoing re-irradiation showed a significant benefit concerning pain relief. Their total outcome was comparable to patients showing a good response from the beginning. No relevant acute or chronic side effects were recorded.

Conclusion

Both patient groups showed good results concerning pain relief. A fractionation schedule of 12 × 0.5?Gy was not superior to the current standard dose of 6 × 1?Gy. Further trials are necessary to explore the best fractionation schedule.

     

Reirradiation + hyperthermia for recurrent breast cancer en cuirasse

Background and purpose

Patients with irresectable locoregional recurrent breast cancer en cuirasse (BCEC) do not have effective curative treatment options. Hyperthermia, the elevation of tumor temperature to 40–45?°C, is a well-established radio- and chemotherapy sensitizer. A total of 196 patients were treated with reirradiation and hyperthermia (reRT+HT) at two Dutch institutes from 1982–2005. The palliative effect was evaluated in terms of clinical outcome and toxicity.

Patients and methods

All patients received previous irradiation to a median dose of 50?Gy. In all, 75% of patients received 1–6 treatment modalities for previous tumor recurrences. ReRT consisted of 8 × 4?Gy given twice a week or 12 × 3?Gy given four times a week. Superficial hyperthermia was added once or twice a week. Tumor area comprised ≥½ of the ipsilateral chest wall.

Results

Overall clinical response rate was 72% (complete response [CR] 30%, partial response [PR] 42%, stable disease [SD] 22%, progressive disease [PD] 6%). The local progression-free rate at 1 year was 24%. Median survival was 6.9 months. Forty-three percent of our patients with CR, PR, SD after treatment remained infield progression-free until death or last follow-up. Acute ≥grade 3 toxicity occurred in 33% of patients, while late ≥grade 3 toxicity was recorded in 14% of patients. Tumor ulceration prior to treatment had a negative impact on both clinical outcome and toxicity.

Conclusion

ReRT+HT provides sustainable palliative tumor control, despite refractory, extensive tumor growth. Compared to currently available systemic treatment options, reRT+HT is more effective with less toxicity.

     

Nonmetastatic pancreatic cancer

Purpose

The role of radiotherapy (RT) for nonmetastatic pancreatic cancer is still a matter of debate since randomized control trials have shown inconsistent results. The current retrospective single-institution study includes both resected and unresected patients with nonmetastasized pancreatic cancer. The aim is to analyze overall survival (OS) after irradiation combined with induction chemotherapy.

Patients and methods

Of the 73 patients with nonmetastatic pancreatic cancer eligible for the present analysis, 42 (58%) patients had adjuvant chemoradiotherapy (CRT), while 31 (42%) received CRT as primary treatment. In all, 65 (89%) had chemotherapy at any time before, during, or after RT, and 39 (53%) received concomitant CRT. The median total dose was 50?Gy (range 12–77?Gy), while 61 (84%) patients received >40?Gy.

Results

With a median follow-up of 22 months (range 1.2–179.8 months), 14 (19%) are still alive and 59 (81%) of the patients have died, whereby 51 (70%) were cancer-related deaths. Median OS and the 2?year survival rate were 22.9 months (1.2–179.8 months) and 44%, respectively. In addition, 61 (84%) patients treated with >40?Gy had a survival advantage (median OS 23.7 vs. 17.3 months, p?=?0.026), as had patients with 4 months minimum of systemic treatment (median OS 27.5 vs. 14.3 months, p?=?0.0004).

Conclusion

CRT with total doses >40?Gy after induction chemotherapy leads to improved OS in patients with nonmetastatic pancreatic cancer.

     

Active raster scanning with carbon ions

Purpose

To evaluate the safety and efficacy of reirradiation with carbon ions in patients with relapse of skull base chordoma and chondrosarcoma.

Patients and methods

Reirradiation with carbon ions was performed on 25 patients with locally recurrent skull base chordoma (n?=?20) or chondrosarcoma (n?=?5). The median time between the last radiation exposure and the reirradiation with carbon ions was 7 years. In the past, 23 patients had been irradiated once, two patients twice. Reirradiation was delivered using the active raster scanning method. The total median dose was 51.0 GyE carbon ions in a weekly regimen of five to six fractions of 3 GyE. Local progression-free survival (LPFS) was evaluated using the Kaplan–Meier method; toxicity was evaluated using the NCI Common Terminology Criteria for Adverse Events (CTCAE v.4.03).

Results

The treatment could be finished in all patients without interruption. In 80?% of patients, symptom control was achieved after therapy. The 2-year-LPFS probability was 79.3?%. A PTV volume of <?100 ml or a total dose of >?51 GyE was associated with a superior local control rate. The therapy was associated with low acute toxicity. One patient developed grade 2 mucositis during therapy. Furthermore, 12?% of patients had tympanic effusion with mild hypacusis (grade 2), while 20?% developed an asymptomatic temporal lobe reaction after treatment (grade 1). Only one patient showed a grade 3 osteoradionecrosis.

Conclusion

Reirradiation with carbon ions is a safe and effective method in patients with relapsed chordoma and chondrosarcoma of the skull base.

     

Use of androgen deprivation and salvage radiation therapy for patients with prostate cancer and biochemical recurrence after prostatectomy

Aim

Overview on the use of androgen deprivation therapy (ADT) added to salvage radiation therapy (SRT) for prostate cancer patients with biochemical recurrence after prostatectomy.

Methods

The German Society of Radiation Oncology (DEGRO) expert panel summarized available evidence published between January 2009 and May 2017, and assessed the validity of the information on outcome parameters including overall survival (OS) and treatment-related toxicity.

Results

Two randomized controlled trials and nine relevant retrospective analyses were identified. The RTOG 9601 trial showed an OS improvement for the combination of 2 years of bicalutamide and SRT compared to SRT alone after a median follow-up of 13 years. This improvement appeared to be restricted to those patients with a prostate specific antigen (PSA) level before SRT of ≥0.7?ng/mL. The GETUG AFU-16 trial showed that after a median follow-up of 5 years, the addition of 6 months of goserelin to SRT improved progression-free survival (PFS; based on biochemical recurrence) as compared to SRT alone. ADT in both trials was not associated with increased major late toxicities. Results of retrospective series were inconsistent with a suggestion that the addition of ADT improved biochemical PFS especially in patients with high-risk factors such as Gleason Score ≥8 and in the group with initially negative surgical margins.

Conclusions

ADT combined with SRT appears to improve OS in patients with a PSA level before SRT of ≥0.7?ng/mL. In patients without persistent PSA after prostatectomy and PSA levels of <0.7?ng/mL, ADT should not routinely be used, but may be considered in patients with additional risk factors such as Gleason Score ≥8 and negative surgical margins.

     

Early inflammatory changes in radiation-induced oral mucositis

Purpose

Early inflammation is a major factor of mucosal reactions to radiotherapy. Pentoxifylline administration resulted in a significant amelioration of radiation-induced oral mucositis in the mouse tongue model. The underlying mechanisms may be related to the immunomodulatory properties of the drug. The present study hence focuses on the manifestation of early inflammatory changes in mouse tongue during daily fractionated irradiation and their potential modulation by pentoxifylline.

Materials and methods

Daily fractionated irradiation with 5 fractions of 3 Gy/week (days 0–4, 7–11) was given to the snouts of mice. Groups of 3 animals per day were euthanized every second day between day 0 and 14. Pentoxifylline (15?mg/kg, s.?c.) was administered daily from day 5 to the day before sacrifice. The expression of the inflammatory proteins TNFα, NF-κB, and IL-1β were analysed.

Results

Fractionated irradiation increased the expression of all inflammatory markers. Pentoxifylline significantly reduced the expression of TNFα and IL-1β, but not NF-κB.

Conclusion

Early inflammation, as indicated by the expression of the inflammatory markers TNFα, NF-κB, and IL-1β, is an essential component of early radiogenic oral mucositis. Pentoxifylline differentially modulated the expression of different inflammatory markers. The mucoprotective effect of pentoxifylline does not appear to be based on modulation of NF-κB-associated inflammation.