Management of interruptions to fractionated radiotherapy treatments: Four and a half years of experience

Background and purposeThe study objective was to report our four-and-a half years experience (March 1 2011–August 15 2015) of a program to manage interruptions in fractionated radiotherapy treatments.MethodsA program was developed, based on a specific database, to manage treatment interruptions. Benefits of the program were analyzed in reference to previously published data. Analysis was also performed of two measures to reduce OTT prolongation and improve treatment outcomes: working on public holidays and conducting treatment unit maintenance on Saturdays.ResultsThe study included 2352 patients. Patients with head and neck cancer obtained the greatest benefit from the program, with a mean increase in TCP of 3.5% and a benefit of at least 4% in 45.6% of them. In prostate cancer patients, the likelihood of biochemical failure was reduced by a mean of 2.0% and was reduced by at least 4% in 19.7% of them. Application of the two proposed measures would have improved the TCP by a mean of 5.4% in head and neck cancer patients. The impact of the compensations program and proposed measures is lesser in the remaining cancer types studied.ConclusionsImplementation of a compensation program has a significant impact on patients with head and neck or prostate cancer but OTT prolongation remains excessive in many treatments. The introduction of fractions on public holidays would assist in the meeting of recommendations for these patients.     

Incidence of radiation toxicity in cervical cancer and endometrial cancer patients treated with radiotherapy alone versus adjuvant radiotherapy

AimThe study was made to evaluate early and late toxicity in a diversified group of patients receiving definitive or adjuvant radiotherapy in terms of clinical diagnosis and treatment methods.BackgroundRadiotherapy is a standard way of treatment in cervical and endometrial cancer patients, both as definitive and adjuvant therapy. But every radiation treatment may be involved with toxicity.Materials and methodsA detailed analysis was performed of 263 patients with gynaecological cancer treated with definitive (90 patients with cervical cancer received radiochemotherapy or radiotherapy exclusively) and adjuvant radiotherapy (38 with cervical and 135 with endometrial cancer).ResultsAcute reactions were found in 51.3% and late reactions were found in 14.8% of patients. It was stated that early (p < 0.007) and late (p < 0.003) post radiation reaction appear more frequently in women treated with definitive than adjuvant radiotherapy. The analysis of the whole group revealed higher rate of toxicity, both early and late, in the gastrointestinal tract than in the urinary system (p < 0.004). Comparing the subgroups, it was found that intestinal reactions occurred more frequently in the definitive radiotherapy group than in the adjuvant one.The occurrence of side effects was associated with the prolongation of total irradiation time due to necessary interruptions of radiotherapy. The comparison of the subgroups showed that interruptions occurred more frequently in patients receiving definitive rather than adjuvant radiotherapy (17.7–2.9%).ConclusionsDefinitive radiotherapy compared with adjuvant treatment may by associated with higher percentage of side effects caused by dose of therapy and correlation with chemotherapy.     

Adyuvant fractionated radiotherapy after resection of intracranial hemangiopericytoma

AimReview of literature and adjuvant treatment in Hemangiopericytoma after complete resection.BackgroundIntracranial hemangiopericytoma (HPC) is an uncommon malignant vascular tumor arising from mesenchymal cells with pericytic differentiation. Surgery remains the mainstay treatment, and adjuvant radiation therapy appears to be appropriate for patients with high grade tumors or incomplete resection. We present our experience and review of the literature.Materials and methodsWe describe two cases of intracranial hemangiopericytoma located in the frontal lobe of the CNS. Both patients underwent complete tumor resection followed by adjuvant fractionated radiotherapy and completed treatment without interruptions.ResultsA local recurrence was observed in one of these cases and fractionated stereotactic radiotherapy was performed. Both patients are alive and disease has been under control up to date.ConclusionThe treatment of choice for intracranial hemangiopericytoma is a complete surgical resection as long as possible. Adjuvant radiotherapy of HPC can result in increased tumor control and should be considered as an effective treatment for patients with high grade or demonstrated residual tumor in the postoperative period. Salvage treatment using limited-field fractionated radiotherapy for local recurrence treatment is considered an acceptable option.     

Combined effects of radiotherapy and photodynamic therapy on an in vitro human prostate model

Human prostate cancer cells were evaluated for growth after photodynamic therapy, radiotherapy, and combined treatment. Indocyanine green was tested as a photosensitizer and radiosensitizer. Two human cell lines were used: PC-3 derived from prostate carcinoma, and EPN derived from normal prostate tissue. The light source used for the photoactivation experiments was a diode laser peaked at 805 nm. The light dose incident on cells was 108 J/cm(2). Ionizing radiation was produced by a linear accelerator, and the dose was 2, 4 and 6 Gy. Cytotoxicity was evaluated by measuring the colony forming ability of cells. Our results show that indocyanine green induces cell death by photoactivation, but it does not act as a radiosensitizer if used with ionizing radiation. The combined treatment of photodynamic therapy and radiotherapy produces an additive effect which does not depend on the sequence of the two treatments. Combined treatments could be more useful since they allow the reduction of the ionizing radiation dose to obtain the same effect as one obtainable by radiotherapy alone.     

Predicting differential responses to structured treatment interruptions during HAART

Highly active antiretroviral therapy (HAART) has been used clinically in various administration schemes for several years. However, due to the development of drug resistance, evolution of viral strains, serious side effects, and poor patient compliance, the combination of drugs used in HAART fails to effectively contain virus long term in a high proportion of patients. Our group and others have suggested a change to the usual regimen of continuous HAART through structured treatment interruptions (STIs). STIs may provide similar clinical benefits as continuous treatment such as reduced viral loads and reestablishment of CD4⁺ T cells while allowing patients drug holidays. We explore the use of STIs using a previously published model that accurately represents CD4⁺ T-cell counts and viral loads during both untreated HIV-1 infection and HAART therapy. We simulate the effects of different STI regimens including weekly and monthly interruptions together with variations in treatment initiation time. We predict that differential responses to STIs as observed in conflicting clinical trial data are impacted by the duration of the interruption, stage of infection at initiation of treatment, strength of the immune system in suppressing virus, or pre-therapy CD4⁺ T-cell count or virus load. Our results indicate that dynamics occurring below the limit of detection (LOD) are influenced by these factors, and contribute to reemergence or suppression of virus during interruptions. Simulations predict that short-term viral suppression with varying interruptions strategies does not guarantee long-term clinical benefit.     

HIV reservoirs and immune surveillance evasion cause the failure of structured treatment interruptions: a computational study

Continuous antiretroviral therapy is currently the most effective way to treat HIV infection. Unstructured interruptions are quite common due to side effects and toxicity, among others, and cannot be prevented. Several attempts to structure these interruptions failed due to an increased morbidity compared to continuous treatment. The cause of this failure is poorly understood and often attributed to drug resistance. Here we show that structured treatment interruptions would fail regardless of the emergence of drug resistance. Our computational model of the HIV infection dynamics in lymphoid tissue inside lymph nodes, demonstrates that HIV reservoirs and evasion from immune surveillance themselves are sufficient to cause the failure of structured interruptions. We validate our model with data from a clinical trial and show that it is possible to optimize the schedule of interruptions to perform as well as the continuous treatment in the absence of drug resistance. Our methodology enables studying the problem of treatment optimization without having impact on human beings. We anticipate that it is feasible to steer new clinical trials using computational models.     

The Impact of the Overall Radiotherapy Time on Clinical Outcome of Patients with Nasopharyngeal Carcinoma; A Retrospective Study

Purpose

In Yogyakarta, nasopharyngeal carcinoma (NPC) shows a poor response to radiotherapy treatment. Previous study showed a prolonged overall treatment time (OTT), due to interruptions during treatment. This study explores the association between clinical outcome and OTT. Secondary, the relation between clinical outcome and disease stage, waiting time to radiation (WT) and chemotherapy schedule was explored.

Methods

In this retrospective cohort, 142 patients who started curative intent radiotherapy for NPC between March 2009 and May 2014, with or without chemotherapy, were included. The median follow up time was 1.9 years. Data was collected on WT, OTT, disease stage, and chemotherapy schedule. Time factors were log-transformed. Clinical outcome was defined as therapy response, loco-regional control (LRC), disease free survival (DFS) and overall survival (OS).

Results

The median WT was 117 days (range 12–581) and OTT was 58 days (43–142). OTT and disease stage were not associated to any of the clinical outcome parameters. The log- WT was associated to poor therapy outcome (HR 1.68; 95% ci: 1.09–2.61), LRC (HR 1.66; 95% ci: 1.15–2.39), and DFS (HR 1.4; 95% ci: 1.09–1.81). In the multivariable analysis, significant hazard risk for poor therapy response, LRC, DFS and OS were seen for patients who didn’t received concurrent chemotherapy.

Conclusion

Not receiving concurrent chemotherapy showed the strongest risk for poor outcome. Since the choice of chemotherapy is related to a variety of factors, like the WT and patient’s physical condition when radiation can start, careful interpretation is needed. Reason for not finding a relation between OTT and clinical outcome might be the low number of patients who finished radiotherapy within 7 weeks, or by a stronger detrimental effect of other factors.     

Clinical management of secondary angiosarcoma after breast conservation therapy

Aim

The aim of this paper is to summarize the treatment outputs of secondary angiosarcoma after breast conservation therapy at St. Eizabeth Cancer Centre, Slovakia.

Background

Angiosarcoma of the breast is a rare but very aggressive malignant tumor of the vascular endothelium, characterized by rapidly proliferating and extensively infiltrating growth. Breast angiosarcoma may occur de novo, or as a complication of radiation therapy, or chronic lymphedema secondary to axillary lymph node dissection for mammary carcinoma. Radiotherapy in the treatment of breast cancer is associated with an increased risk of subsequent sarcoma.

Materials and methods

Retrospective study of medical records from the cancer databases was done in order to analyze the secondary breast angiosarcoma. This disease is an iatrogenic condition that warrants close follow-up and judicial use of radiotherapy in breast conserving therapy. Therefore, it is more prevalent in cases treated with radiotherapy, occurring especially in or adjacent to the radiation field. Clinical histories and follow-up data of identified patients after breast conservation therapy of invasive breast cancer were reviewed. In addition, a comprehensive literature review on diagnosis and treatment procedures was done in order to summarize state-of-the-art clinical approach.

Results and discussions

Three cases of secondary angiosarcoma after breast conservation therapy (BCT) were identified among 4600 patients treated at St. Elizabeth Cancer Institute during previous 16 years (1995–2011). Secondary breast angiosarcoma was diagnosed in a median period of 11 years following primary radiotherapy, median age at the time of diagnosis was 75 years. Surgical treatment consisted of radical mastectomy. The first patient, a 56-year-old woman received neoadjuvant chemotherapy (docetaxel + gemcitabin), second one (75 year) was treated by radiotherapy (TD 26 Gy, 2 Gy per fraction), since chemotherapy was not indicated. The last patient (80 year) got adjuvant chemotherapy (paclitaxel). Average follow up of the patients was 31 months. As of 31 July 2012, our patients were doing well without evidence of recurrent disease after treatment.

Conclusions

Angiosarcoma remains a difficult management problem with poor loco-regional and distal control. In our study, an overall incidence rate of secondary breast angiosarcoma is 0.065%. Although the prognosis for this disease is poor (typical survival period is 14.5–34 months with a 5-year survival rate of approximately 15%), all the three patients treated at our institute are alive and disease-free at the end of reported period. Finally, it is assumed that the use of breast conserving therapy will increase the incidence of post-irradiation angiosarcoma but the small difference in risk of subsequent sarcoma of the breast cancer patients receiving radiotherapy does not suppress its benefit.     

基于RNA的抗HIV-1基因治疗方法研究进展

艾滋病自发现以来在全球范围内迅速蔓延,危害性极高,目前广泛采用的高效抗逆转录病毒疗法(HAART)虽能够显著提高HIV-1感染者生活质量,但存在着价格昂贵,耐药和副作用的问题经常会导致HAART治疗的中断。要获得长期持续的抗病毒治疗效果还有待于研发新的抗病毒药物和治疗方法。近年来随着分子生物技术、干细胞研究、纳米技术等相关技术的发展,关于抗HIV-1基因治疗方法的研究受到了广泛关注。主要针对基于RNA的抗HIV-1基因治疗方法,包括反义RNA、核酶、RNA诱饵以及RNA干扰技术在抗HIV-1基因治疗方面进行综述。研究表明,以RNA为基础的抗HIV-1基因治疗方法有望成为传统治疗方法的一种有效辅助手段。     

Floral Inhibition of Biloxi Soybean During a 72-hour Cycle

The inhibitory effect of light interruptions given during the photophobe phases of a 72-hour cycle was studied with Biloxi soybean [Glycine max (L.) Merr.]. The basic 72-hour cycle consisted of 8 hours of light followed by 64 hours of darkness and was repeated 7 times. Supplementary white light treatments given at the twenty-fourth and/or forty-eighth hour of the cycle (photophil phases) promoted the flowering levels of the controls and kept light treatments given at the most inhibitory points from inhibiting flowering completely. Such supplementary light treatments did not affect the time of maximum sensitivity to light interruptions. When 30-minute light breaks were used, maximum inhibition occurred at the 16-, 43-, and 63-hour points. The duration of the light breaks affected the time of maximum inhibition when given during the second photophobe phase. The time of maximum inhibition occurred earlier with 4-hour light breaks than with either 3-minute or 2-hour light interruptions.

Three-minute red light interruptions produced essentially the same effect as 3-minute white light interruptions. Such treatments inhibited flowering completely in the first photophobe phase, inhibited flowering to only a small degree in the second photophobe phase, and inhibited flowering to an intermediate degree in the third photophobe phase. Far-red light interruptions strongly inhibited flowering in the first photophobe phase, especially when given early in the dark period. Three minutes of supplementary white light given at the twenty-fourth or forty-eighth hour of the cycle partially overcame the inhibitory effect of far-red light. Four hours of supplementary white light at these times completely overcame the far-red inhibition.

     

立体定向适形放疗在早期肝癌治疗中的应用

目的:探讨立体定向适形放疗对早期肝癌患者临床疗效的影响。方法:回顾性分析我院2008年5月~2011年5月收治的190例早期肝癌患者,按照其治疗方式分为放疗组(n=95)及化疗组(n=95),2组患者分别接受立体定向适形放疗及肝动脉化疗栓塞治疗,比较患者的临床疗效。结果:2组患者治疗前后WBC、RBC、PLT、TBIL、ALT、PT指标均未见明显变化(P0.05);2组患者治疗后AFP、TMD均显著降低,放疗组降低程度更为明显(P0.05);放疗组总有效率为69.48%,显著高于化疗组的43.16%(P0.05)。2组患者治疗期间均发生胃肠道反应等并发症,经对症处理后症状消失,均未见其他严重并发症发生;2组患者1年复发率、1年生存率及2年生存率无明显统计学差异(P0.05);放疗组2年、3年复发率显著低于对照组,其3年生存率显著高于化疗组(P0.05)。结论:立体定向适形放疗能够有效降低早期肝癌患者AFP水平,缩小其肿瘤直径,具有良好的临床疗效,且该方案对患者血液指标、机体状态影响较小,具有良好的安全性,是保障医疗质量、改善患者预后的有效手段。     

Viral Dynamics during Structured Treatment Interruptions of Chronic Human Immunodeficiency Virus Type 1 Infection

Although antiviral agents which block human immunodeficiency virus (HIV) replication can result in long-term suppression of viral loads to undetectable levels in plasma, long-term therapy fails to eradicate virus, which generally rebounds after a single treatment interruption. Multiple structured treatment interruptions (STIs) have been suggested as a possible strategy that may boost HIV-specific immune responses and control viral replication. We analyze viral dynamics during four consecutive STI cycles in 12 chronically infected patients with a history (>2 years) of viral suppression under highly active antiretroviral therapy. We fitted a simple model of viral rebound to the viral load data from each patient by using a novel statistical approach that allows us to overcome problems of estimating viral dynamics parameters when there are many viral load measurements below the limit of detection. There is an approximate halving of the average viral growth rate between the first and fourth STI cycles, yet the average time between treatment interruption and detection of viral loads in the plasma is approximately the same in the first and fourth interruptions. We hypothesize that reseeding of viral reservoirs during treatment interruptions can account for this discrepancy, although factors such as stochastic effects and the strength of HIV-specific immune responses may also affect the time to viral rebound. We also demonstrate spontaneous drops in viral load in later STIs, which reflect fluctuations in the rates of viral production and/or clearance that may be caused by a complex interaction between virus and target cells and/or immune responses.     

Erratum to: “Pancreatic cancer and SBRT: A new potential option?” [Rep. Pract. Oncol. Radiother. 20 (2015) 377–384]

Local control remains a major issue for patients with unresectable, locally advanced pancreatic cancer (LAPC). The role of radiation therapy in the management of LAPC represents an area of some controversy. Stereotactic body radiotherapy is an emerging treatment option for LAPC as it can provide a therapeutic benefit with significant advantages for patients’ quality of life over standard conventional chemoradiation. The objective of this review is to present the rationale for stereotactic body radiotherapy in LAPC, as well as to discuss the potential limitations and caveats of the currently available studies.     

Fertilité et aneuploïdies spermatiques après traitement par radiothérapie et/ou chimiothérapie pour cancer du testicule ou lymphome

Improvements in cancer therapy have considerably modified patient survival rates over recent years. However, the side effects of these treatments especially the effects on fertility, must be taken into account. Anticancer therapy can transiently inhibit spermatogenesis. Factors such as pretreatment semen parameters and the type of chemotherapy or radiotherapy may influence recovery of spermatogenesis, but it is still impossible to predict the probability of and time to recovery for each patient. Sperm banking remains the only way to prevent the effects of cancer treatment on male fertility. Another possible effect of chemotherapy or radiotherapy is genetic damage to germ cells. For instance, chromosomal abnormalities in viable sperm produced by these patients after recovery of spermatogenesis may result in fetal death or congenital abnormalities in their offspring. It has been fairly well documented that, during the first three months after treatment, DNA breaks and abnormal chromosomal segregation induced by chemotherapy/radiotherapy lead to structural and numerical chromosomal abnormalities in spermatozoa, respectively. However, the long-term effects on genetic sperm content have not been clearly established. The results of published studies are contradictory and are based on limited numbers of patients (maximum of 6). We present the preliminary results of a retrospective study concerning patients treated for testicular cancer or lymphoma between 1995 and 2000. Fluorescence in situ hybridization (FISH) analysis of chromosomes X, Y and 18 was performed on sperm collected one to five years after treatment and compared to the data obtained for non-affected fertile men. For four out of 13 patients, we found a significantly increased frequency of aneuploidy rates (mainly XY disomy and diploidy), and these results did not appear to be correlated with sperm count, sperm morphology or post-treatment duration. In conclusion, increased sperm aneuploidy rates appear to only concern a small number of patients, to varying degrees and without any predictive factors. According to published data and our preliminary results, we recommend waiting at least two years before starting ART (Assisted Reproduction Therapy) for patients treated for testicular cancer or lymphoma. Moreover, FISH analysis could be helpful to choose between ART with post-treatment sperm or cryopreserved sperm.     

Pancreatic cancer and SBRT: A new potential option?

Local control remains a major issue for patients with unresectable, locally advanced pancreatic cancer (LAPC). The role of radiation therapy in the management of LAPC represents an area of some controversy. Stereotactic body radiotherapy is an emerging treatment option for LAPC as it can provide a therapeutic benefit with significant advantages for patients’ quality of life over standard conventional chemoradiation. The objective of this review is to present the rationale for stereotactic body radiotherapy in LAPC, as well as to discuss the potential limitations and caveats of the currently available studies.     

In vivo dosimetry for lung radiotherapy including SBRT

SBRT for lung cancer is being rapidly adopted as a treatment option in modern radiotherapy centres. This treatment is one of the most complex in common clinical use, requiring significant expertise and resources. It delivers a high dose per fraction (typically ∼6–30 Gy/fraction) over few fractions. The complexity and high dose delivered in only a few fractions make powerful arguments for the application of in vivo dosimetry methods for these treatments to enhance patient safety. In vivo dosimetry is a group of techniques with a common objective – to estimate the dose delivered to the patient through a direct measurement of the treatment beam(s). In particular, methods employing an electronic portal imaging device have been intensely investigated over the past two decades. Treatment verification using in vivo dosimetry approaches has been shown to identify errors that would have been missed with other common quality assurance methods. With the addition of in vivo dosimetry to verify treatments, medical physicists and clinicians have a higher degree of confidence that the dose has been delivered to the patient as intended.In this review, the technical aspects and challenges of in vivo dosimetry for lung SBRT will be presented, focusing on transit dosimetry applications using electronic portal imaging devices (EPIDs). Currently available solutions will be discussed and published clinical experiences, which are very limited to date, will be highlighted.     

The future of Radiation Oncology: Considerations of Young Medical Doctor

Radiation therapy plays an increasingly important role in the management of cancer. Currently, more than 50% of all cancer patients can expect to receive radiotherapy during the course of their disease, either in a primary management (radical or adjuvant radiotherapy) or for symptom control (palliative radiotherapy).Radiation oncology is a very unique branch of medicine connected with clinical knowledge and also with medical physics. In recent years, this approach has become increasingly absorbed with technological advances. This increasing emphasis on technology, together with other important changes in the health-care economic environment, now place the specialty of radiation oncology in a precarious position. New treatment technologies are evolving at a rate unprecedented in radiation therapy, paralleled by improvements in computer hardware and software. These techniques allow assessment of changes in the tumour volume and its location during the course of therapy (interfraction motion) so that re-planning can adjust for such changes in an adaptive radiotherapy process.If radiation oncologists become simply the guardians of a single therapeutic modality they may find that time marches by and, while the techniques will live on, the specialty may not. This article discusses these threats to the field and examines strategies by which we may evolve, diversify, and thrive.     

Treatment of localized extranodal NK/T cell lymphoma,nasal type: a systematic review

Extranodal natural killer/T cell lymphoma (ENKTL), nasal type, presents predominantly as a localized disease involving the nasal cavity and adjacent sites, and the treatment of localized nasal ENKTL is a major issue. However, given its rarity, there is no standard therapy based on randomized controlled trials and therefore a lack of consensus on the treatment of localized nasal ENKTL. Currently recommended treatments are based mainly on the results of phase II studies and retrospective analyses. Because the previous outcomes of anthracycline-containing chemotherapy were poor, non-anthracycline-based chemotherapy regimens, including etoposide and l-asparaginase, have been used mainly for patients with localized nasal ENKTL. Radiotherapy also has been used as a main component of treatment because it can produce a rapid response. Accordingly, the combined approach of non-anthracycline-based chemotherapy with radiotherapy is currently recommended as a first-line treatment for localized nasal ENKTL. This review summarizes the different approaches for the use of non-anthracycline-based chemotherapy with radiotherapy including concurrent, sequential, and sandwich chemoradiotherapy, which have been proposed as a first-line treatment for newly diagnosed patients with localized nasal ENKTL.     

Medical physics in radiotherapy: The importance of preserving clinical responsibilities and expanding the profession's role in research,education, and quality control

Medical physicists have long had an integral role in radiotherapy. In recent decades, medical physicists have slowly but surely stepped back from direct clinical responsibilities in planning radiotherapy treatments while medical dosimetrists have assumed more responsibility. In this article, I argue against this gradual withdrawal from routine therapy planning. It is essential that physicists be involved, at least to some extent, in treatment planning and clinical dosimetry for each and every patient; otherwise, physicists can no longer be considered clinical specialists. More importantly, this withdrawal could negatively impact treatment quality and patient safety. Medical physicists must have a sound understanding of human anatomy and physiology in order to be competent partners to radiation oncologists. In addition, they must possess a thorough knowledge of the physics of radiation as it interacts with body tissues, and also understand the limitations of the algorithms used in radiotherapy. Medical physicists should also take the lead in evaluating emerging challenges in quality and safety of radiotherapy. In this sense, the input of physicists in clinical audits and risk assessment is crucial. The way forward is to proactively take the necessary steps to maintain and advance our important role in clinical medicine.     

Prospective study on the influence of radiochemotherapy on pituitary function in children with acute leukaemia and NHL.

To assess effects of chemo- and radiotherapy on the endocrine system 31 children with acute leukaemia and NHL (3 AML, 24 ALL, 4 NHL) were investigated. Children were treated according to modified BFM protocols. 25 patients were before, 5 during and one after puberty (2 to 16 y.). Before treatment, during induction therapy, during cranial irradiation, 4-6 weeks later and during maintenance therapy the following hormone values were estimated: TSH and prolactin basal and 30 min. after TRH (5 micrograms/kg i.v.), LH and FSH basal. Final investigations included total T4 and T3. In conclusion, chemo- und radiotherapy lead to transient elevations of TSH and prolactin in a few patients, but without proof for permanent disorders. Due to the fact all 3 patients with hyperprolactinaemia showed high prolactin levels (700 to 770 mU/l) already before treatment it is unlikely therapy was the main cause of these observed alterations. Although basal LH and FSH values were in normal ranges for age the increasing values after cranial irradiation in prepubertal children may reflect a possible initiation of early maturation, reported by others. Furthermore a retrospective growth study was performed in children treated with 2 different protocols. Protocol LSA2L2 used in the past before 1981 resulted in a permanent reduction of the height. In contrast, the mean SDS for height in children treated with protocol VII declined only during the intensive period of treatment. A catch-up growth occured already during maintenance therapy. Prophylactic cranial irradiation with 18 Gy in our patients under protocol LSA2L2 did not affect growth during the first 5 years after diagnosis.