Image guided radiotherapy in curative treatment for prostate cancer. 5-year results from a randomized controlled trial (RIC-trial).

BACKGROUND: Between 2012 and 2015 we conducted a randomized controlled trial in prostate cancer patients comparing weekly 2-D portal imaging versus daily 3-D verification. AIM: To evaluate the clinical outcomes of image guided radiotherapy by presenting rectal and urinary side effects, health related quality of life and progression free survival after 5-years follow up of a randomized controlled trial. METHODS: We randomized 260 men with intermediate or high-risk prostate cancer to weekly 2-D portal imaging with 15 mm margin from CTV to PTV (Arm A) or daily 3-D cone-beam computer tomography with 7 mm margins (Arm B). Prescribed doses were 78 Gy/39 fractions. All patients received hormonal therapy. Primary end point was patient reported bowel symptoms and secondary outcomes were patient reported urinary symptoms, health- related quality of life and progression free survival. RESULTS: Of the 216 patients available for analyses at 5 years more than 90 % completed patient reported outcome measures. There were no significant differences between study arms for any single items nor scales evaluating bowel symptoms. There were also no differences in self-reported urinary symptoms nor in health-related quality of life. Symptom scores were low in both study arms. Progression free survival was similar in Arm B as compared to arm A (Hazard ratio 1.01; 95 % CI 0.57 to 1.97). CONCLUSIONS: Our results support that both 2-D weekly and 3-D daily image guided radiotherapy are safe and efficient treatments for PC and emphasize the need to evaluate technological progress in clinical trials with long follow-up.

Safer and More Convenient Modern Curative Radiotherapy for Patients With Early Prostate Cancer.

BACKGROUND/AIM: New fractionation schedules with modern tools are a very rapidly developing area in curative radiotherapy (RT) for early prostate cancer (PC). To apply these techniques in everyday clinical practice, we planned this phase II trial with different fractionation schedules and followed up patients using careful health-related quality of life (QoL) questionnaires for three years. PATIENTS AND METHODS: Seventy-three PC patients with one or two intermediate PC risk factors according to the National Comprehensive Cancer Network criteria were recruited. Forty-two patients were treated with 78/2 Gy (conventional fractionation, CF) or 60/3 Gy (moderately hypofractionation RT, MHF), and 31 patients were treated with 36.25/7.25 Gy (stereotactic body RT, SBRT). Their PSA levels were measured, and QoL data were assessed for genitourinary (GU), gastrointestinal (GI), and sexual well-being between the baseline and three years after treatment. A Rectafix™ (RF) fixation device was used in 30 patients in the CF/MHF group. RESULTS: Three years after radiotherapy (RT), there were no differences between the groups regarding GU, GI, sexual well-being, PSA response, or clinical outcomes. On QoL questionnaires, men in the SBRT group were more satisfied with their QoL at the end of RT. Urinary symptoms (p=0.004) and urinary incontinence were more common in the CF/MHF group (p=0.016) three months after RT. The use of RF reduced GI toxicity, especially urgency (p=0.002), at three years after RT. CONCLUSION: Modern, short, five-fraction stereotactic radiotherapy as a local curative treatment for PC is well tolerated and safe. Our novel results showing a decrease in GI toxicity using Rectafix™ fixation should be confirmed in future randomized trials.

Late adverse events in patients with pelvic cancer after oncologic treatment-intervention and treatment effect.

PURPOSE: Few studies have focused on the late adverse events after oncologic treatment in pelvic cancer patients. Here, the treatment effect/interventions were studied on late side effects as GI, sexual, and urinary symptoms in pelvic cancer patients who visited a highly specialized rehabilitation clinic in Linköping. METHODS: This retrospective longitudinal cohort study included 90 patients who had at least one visit at the rehabilitation clinic for late adverse events at Linköping University hospital between 2013 to 2019. The toxicity of the adverse events was analyzed by using the common terminology criteria for adverse events (CTCAE). RESULTS: By comparing the toxicity of symptoms between visits 1 and 2, we showed that the GI symptoms decreased with 36.6% (P = 0.013), the sexual symptoms with 18.3% (P < 0.0001), and urinary symptoms with 15.5% (P = 0.004). Patients who received bile salt sequestrant had a significant improvement in grade of GI symptoms as diarrhea/fecal incontinence at visit 2 compared to visit 1 where 91.3% were shown to have a treatment effect (P = 0.0034). The sexual symptoms (vaginal dryness/pain) significantly improved due to local estrogens between visits 1 and 2 where 58.1% had a reduction of symptoms (P = 0.0026). CONCLUSION: The late side effects as GI, sexual, and urinary symptoms was significantly reduced between visits 1 and 2 at the specialized rehabilitation center in Linköping. Bile salt sequestrants and local estrogens are effective treatments for side effects as diarrhea and vaginal dryness/pain.

Chemotherapy and Radiotherapy Long-Term Adverse Effects on Oral Health of Childhood Cancer Survivors: A Systematic Review and Meta-Analysis.

The survival rate for pediatric cancer has increased over the past few decades, short- and long-term complications have been detected and studied, and oral complications have emerged as an important topic of research. Here, we aimed to highlight the importance of oral manifestations that may only become apparent years or even decades after cancer treatment. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. We searched articles using PubMed via the MEDLINE, Web of Science, and LILACS databases until October 2023. Overall, 35 observational studies were included, and the results estimated a pooled prevalence of the following dental anomalies: discoloration, 53%; crown-root malformations and agenesis, 36%; enamel hypoplasia, 32%; root development alterations, 29%; unerupted teeth, 24%; microdontia, 16%; hypodontia, 13%; and macrodontia, 7%. Most childhood cancer survivors have at least one dental sequela. Childhood cancer survivors presented a higher risk of having dental alterations than control counterparts. Additional analyses reveal possible sex-based differences that should be explored in future studies. These results collectively highlight the importance of oral healthcare and the prevention of disease in childhood cancer survivors.

[Physical long-term consequences of cancer]. / Körperliche Langzeitfolgen von Krebserkrankungen.

The number of long-term survivors of malignant diseases is steadily increasing, which is due to the further development and optimization of multimodal therapy strategies and the mechanisms of new substance classes. These can now be combined with classical treatment methods or used sequentially. At the same time the number of patients who suffer from physical and psychosocial long-term consequences of cancer therapies or have to live with chronic side effects under the long-term therapies increases. Every therapy, whether radiation, chemotherapy, targeted therapy, or operation, has undesirable long-term side effects that contribute to the decrease of one's quality of life. These affect all parts of the body. As a result, patients can be heavily burdened. In oncology and in other disciplines involved in aftercare, these consequences must therefore be increasingly addressed and clarified and treatment strategies further developed. Unfortunately, there is still a considerable need for research in this area; moreover, there is a lack of clinical studies examining the evidence of a wide variety of holistic therapy methods.

Patient-reported QoL in anal cancer survivors 3 and 6 years after treatment-results from the Swedish national ANCA study.

PURPOSE: The impact of anal cancer treatment for the patients is best evaluated by the patients themselves. The purpose of this study was to investigate quality of life (QoL) in patients with anal cancer at 3 and 6 years after treatment. METHODS: A Swedish national cross-sectional prospective cohort study with patients diagnosed with anal cancer between 2011 and 2013. Patients were invited to respond to a QoL questionnaire at 3 and 6 years, with focus on bowel, urinary and sexual function, social and mental function, co-morbidity, lifestyle, daily activities, personal characteristics, and perceived QoL. It also contained questions on the severity of the symptoms regarding occurrence, frequency, and duration and the level of "bother" experienced related to functional symptoms. QoL and prevalence of bother with urinary, sexual, bowel dysfunction, and anal pain were described. The prevalence of impaired QoL was compared with a healthy reference population. The association between QoL and experiencing bother was quantified by regression models. RESULTS: From an original cohort of 464 patients with anal cancer, 264 (57%) were alive and contacted at 3 years and 230 (50%) at 6 years. One hundred ninety-five (74%) patients responded to the 3-year and 152 (66%) to the 6-year questionnaire. Sixty percent reported low QoL at both 3 and 6 years. Impaired QoL was more prevalent among patients with major bother due to bowel dysfunction (at 3 years RR 1.42, 95% CI (1.06-1.9) p-value 0.020, at 6 years RR 1.52, 95% CI (1.03-2.24) p-value 0.034) and urinary dysfunction (at 6 years RR 1.44, 95% CI (1.08-1.91) p-value 0.013). There was a tendency to a positive relationship between the number of bodily functions causing bother and risk for impaired QoL. CONCLUSION: Patients treated for anal cancer reported bother regarding several bodily functions as well as poor QoL both at 3 and 6 years without much improvement. Bother was also associated with low QoL indicating that function-related bother should be addressed.

Re-Irradiation for Head and Neck Cancer: Cumulative Dose to Organs at Risk and Late Side Effects.

Re-irradiation in head and neck cancer is challenging, and cumulative dose constraints and dose/volume data are scarce. In this study, we present dose/volume data for patients re-irradiated for head and neck cancer and explore the correlations of cumulative dose to organs at risk and severe side effects. We analyzed 54 patients re-irradiated for head and neck cancer between 2011 and 2017. Organs at risk were delineated and dose/volume data were collected from cumulative treatment plans of all included patients. Receiver-operator characteristics (ROC) analysis assessed the association between dose/volume parameters and the risk of toxicity. The ROC-curve for a logistic model of carotid blowout vs. maximum doses to the carotid arteries showed AUC = 0.92 (95% CI 0.83 to 1.00) and a cut-off value of 119 Gy (sensitivity 1.00/specificity 0.89). The near-maximum dose to bones showed an association with the risk of osteoradionecrosis: AUC = 0.74 (95% CI 0.52 to 0.95) and a cut-off value of 119 Gy (sensitivity 1.00/specificity 0.52). Our analysis showed an association between cumulative dose to organs at risk and the risk of developing osteoradionecrosis and carotid blowout, and our results support the existing dose constraint for the carotid arteries of 120 Gy. The confirmation of these dose-response relationships will contribute to further improvements of re-irradiation strategies.

Modelling of late side-effects following cranial proton beam therapy.

BACKGROUND: The limited availability of proton beam therapy (PBT) requires individual treatment selection strategies that can be based on normal tissue complication probability (NTCP) models. We developed and externally validated NTCP models for common late side-effects following PBT in brain tumour patients to optimise patients' quality of life. METHODS: Cohorts from three PBT centres (216 patients) were investigated for several physician-rated endpoints at 12 and 24 months after PBT: alopecia, dry eye syndrome, fatigue, headache, hearing and memory impairment, and optic neuropathy. Dose-volume parameters of associated normal tissues and clinical factors were used for logistic regression modelling in a development cohort. Statistically significant parameters showing high area under the receiver operating characteristic curve (AUC) values in internal cross-validation were externally validated. In addition, analyses of the pooled cohorts and of time-dependent generalised estimating equations including all patient data were performed. RESULTS: In the validation study, mild alopecia was related to high dose parameters to the skin [e.g. the dose to 2% of the volume (D2%)] at 12 and 24 months after PBT. Mild hearing impairment at 24 months after PBT was associated with the mean dose to the ipsilateral cochlea. Additionally, the pooled analyses revealed dose-response relations between memory impairment and intermediate to high doses to the remaining brain as well as D2% of the hippocampi. Mild fatigue at 24 months after PBT was associated with D2% to the brainstem as well as with concurrent chemotherapy. Moreover, in generalised estimating equations analysis, dry eye syndrome was associated with the mean dose to the ipsilateral lacrimal gland. CONCLUSION: We developed and in part validated NTCP models for several common late side-effects following PBT in brain tumour patients. Validation studies are required for further confirmation.

Parotid sparing and quality of life in long-term survivors of locally advanced head and neck cancer after intensity-modulated radiation therapy.

PURPOSE: Intensity-modulated radiation therapy (IMRT) enables radiation oncologists to optimally spare organs at risk while achieving homogeneous dose distribution in the target volume. Despite great advances in technology, xerostomia is one of the most detrimental long-term side effects after multimodal therapy in patients with locally advanced head and neck cancer (HNC). This prospective observational study examines the effect of parotid sparing on quality of life in long-term survivors. PATIENTS AND METHODS: A total of 138 patients were grouped into unilateral (n = 75) and bilateral (n = 63) parotid sparing IMRT and questioned at 3, 24, and 60-month follow-up using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-H&N35 questionnaires. Treatment-related toxicity was scored according to the RTOG/EORTC toxicity criteria. Patients' QoL 24 and 60 months after IMRT was analyzed by ANCOVA using baseline QoL (3 months after IMRT) as a covariate. RESULTS: Patients with bilateral and unilateral parotid-sparing IMRT surviving 60 months experience similar acute and late side effects and similar changes in QoL. Three months after IMRT, physical and emotional function as well as fatigue, nausea and vomiting, pain, dyspnea, and financial problems are below (function scales) or above (symptom scales) the threshold of clinical importance. In both groups, symptom burden (EORTC H&N35) is high independent of parotid sparing 3 months after IMRT and decreases over time in a similar pattern. Pain and financial function remain burdensome throughout. CONCLUSION: Long-term HNC survivors show a similar treatment-related toxicity profile independent of unilateral vs. bilateral parotid-sparing IMRT. Sparing one or both parotids had no effect on global QoL nor on the magnitude of changes in function and symptom scales over the observation period of 60 months. The financial impact of the disease and its detrimental effect on long-term QoL pose an additional risk to unmet needs in this special patient population. These results suggest that long-term survivors need and most likely will benefit from early medical intervention and support within survivorship programs.

Late Side Effects in Normal Mouse Brain Tissue After Proton Irradiation.

Radiation-induced late side effects such as cognitive decline and normal tissue complications can severely affect quality of life and outcome in long-term survivors of brain tumors. Proton therapy offers a favorable depth-dose deposition with the potential to spare tumor-surrounding normal tissue, thus potentially reducing such side effects. In this study, we describe a preclinical model to reveal underlying biological mechanisms caused by precise high-dose proton irradiation of a brain subvolume. We studied the dose- and time-dependent radiation response of mouse brain tissue, using a high-precision image-guided proton irradiation setup for small animals established at the University Proton Therapy Dresden (UPTD). The right hippocampal area of ten C57BL/6 and ten C3H/He mice was irradiated. Both strains contained four groups (nirradiated = 3, ncontrol = 1) treated with increasing doses (0 Gy, 45 Gy, 65 Gy or 85 Gy and 0 Gy, 40 Gy, 60 Gy or 80 Gy, respectively). Follow-up examinations were performed for up to six months, including longitudinal monitoring of general health status and regular contrast-enhanced magnetic resonance imaging (MRI) of mouse brains. These findings were related to comprehensive histological analysis. In all mice of the highest dose group, first symptoms of blood-brain barrier (BBB) damage appeared one week after irradiation, while a dose-dependent delay in onset was observed for lower doses. MRI contrast agent leakage occurred in the irradiated brain areas and was progressive in the higher dose groups. Mouse health status and survival corresponded to the extent of contrast agent leakage. Histological analysis revealed tissue changes such as vessel abnormalities, gliosis, and granule cell dispersion, which also partly affected the non-irradiated contralateral hippocampus in the higher dose groups. All observed effects depended strongly on the prescribed radiation dose and the outcome, i.e. survival, image changes, and tissue alterations, were very consistent within an experimental dose cohort. The derived dose-response model will determine endpoint-specific dose levels for future experiments and may support generating clinical hypotheses on brain toxicity after proton therapy.

Addition of chemotherapy to hyperfractionated radiotherapy in advanced head and neck cancer-a meta-analysis.

BACKGROUND: Adding concurrent chemotherapy (CTx) to definitive radiation therapy (RT) in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) improves overall survival. A comparable effect has been reported for hyperfractionated radiotherapy (HFX-RT) alone. Adding concurrent CTx to HFX-RT has been investigated in multiple trials, yet an evident effect on oncological outcomes and toxicity profile has not been established to date. Thus, the aim of the current study was to perform a meta-analysis on the clinical outcome and toxicity of the addition of CTx to HFX-RT. PATIENTS AND METHODS: We performed a literature search for randomized controlled trials comparing HFX-RT alone to HFX-RT + concurrent CTx in patients with LA-HNSCC undergoing definite RT. A meta-analysis was performed using the event rates and effect-sizes for overall survival (OS), progression-free survival (PFS), cancer-specific survival (CSS), distant metastasis-free survival and distant recurrence-free interval (DMFS/DMFI) and locoregional recurrence (LRR) as investigated endpoints. Furthermore, we compared selected acute and late toxicities in the included studies. Statistical analysis was performed using the Microsoft Excel (Microsoft, Redmont, WA, USA) add-in MetaXL 5.3 (EpiGear International, Sunrise Beach, Australia), utilizing the inverse variance heterogeneity model. RESULTS: We identified six studies (n = 1280 patients) randomizing HFX-RT alone and the concurrent addition of CTx. OS was significantly improved in the HFX-RT + CTx group (HR = 0.77, CI95% = 0.66-0.89; p = <0.001). We found similar results in PFS (HR = 0.74, CI95% = 0.63-0.87; p < 0.001) and CSS (HR = 0.72, CI95% = 0.60-0.88; p = 0.001). In contrast, acute toxicities (≥grade 3 mucositis, ≥grade 3 dysphagia) and late adverse events including ≥grade 3 xerostomia, ≥grade 3 subcutaneous, ≥grade 3 bone, ≥grade 3 skin toxicity, and ≥grade 3 dysphagia did not significantly differ between the two groups. CONCLUSION: The addition of CTx to HFX-RT in the definitive treatment of advanced LA-HNSCC improves OS, CSS, PFS, and LRR without a significant increase in high-grade acute and late toxicities.

Late side effects of 3T MRI-guided 3D high-dose rate brachytherapy of cervical cancer : Institutional experiences.

PURPOSE: This article reports experiences with 3T magnetic resonance imaging(MRI)-guided brachytherapy (BT) for cervical cancer focusing on late side effects. METHODS: Between June 2012 and March 2017 a total of 257 uterovaginal BT administrations were performed in 61 consecutive patients with inoperable cervical cancer. All patients were treated with BT combined with external beam radiotherapy. RESULTS: The mean HR-CTV (high risk-clinical target volume) D90 was 87 ± 5.1 Gy equivalent dose corresponding to the conventional fractionation using 2 Gy per fraction (EQD2, range 70.7-97.9 Gy). The mean doses in OAR (organs at risk), namely rectum, sigmoid and bladder were D2 cm3rectum = 62.6 ± 6.9 Gy EQD2 (range 38.2-77.2 Gy), D2 cm3sigmoid = 66.2 ± 6.8 Gy EQD2 (43.2-78.6 Gy) and D2 cm3bladder = 75.1 ± 8.3 Gy EQD2 (58.2-92.6 Gy). There were no signs of late gastrointestinal (GI) toxicity in 49 patients, grade 3 toxicity was seen in 2 patients and grade 4 toxicity in 3 patients. There were no signs of late genitourinary (GU) toxicity in 41 patients, grade 3 toxicity was seen in 4 patients and no signs of grade 4 toxicity were seen. After the treatment, 60 patients (98.4%) achieved locoregional remission. In 54 patients (88.5%) the remission was complete, whereas in 6 patients (9.8%) remission was partial. CONCLUSION: The use of 3T MRI-guided BT leads to achievement of high rates of local control with limited late morbidity as demonstrated in this series of patients.

Female sexual problems after treatment for colorectal cancer - a population-based study.

AIM: There has been limited focus on female sexuality after treatment for colorectal cancer. The aim of this study was to investigate long-term female sexual dysfunction in disease-free colorectal cancer survivors in the Danish population. METHOD: All female Danish patients treated for colorectal cancer between 2001 and 2014 were included if they reported to have been sexually active at the time of diagnosis. They were requested to answer the validated Sexual Vaginal Changes Questionnaire. RESULTS: A total of 2402 patients were included for analysis (43%). Overall, rectal cancer patients reported more sexual inactivity and problems compared to colon cancer patients, but there were no differences in any sexual function domains when excluding irradiated patients and patients with a permanent stoma. A permanent stoma was associated with sexual inactivity [OR 2.56 (95% CI 1.42-4.70)] and overall sexual dysfunction [OR 2.95 (95% CI 1.05-6.38)] in colon cancer patients, as well as inactivity [OR 1.43 (95% CI 1.01-2.04)] and overall dysfunction [OR 2.0 (95% CI 1.18-3.41)] in rectal cancer patients. Furthermore, a permanent stoma was associated with dyspareunia [OR 2.17 (95% CI 1.39-3.38)] and reduced vaginal dimension [OR 3.16 (95% CI 1.99-5.01)]. In rectal cancer patients, radiotherapy exposure increased the odds for overall sexual dysfunction [OR 1.80 (95% CI 1.02-3.16)] and was associated with dyspareunia [OR 1.72 (95% CI 0.95-3.12)]. CONCLUSION: Sexual problems after treatment of colorectal cancer are common. Major risk factors are a permanent stoma and radiotherapy. Relevant patients should be offered professional counselling and treatment.

Impact of Hematopoietic Stem Cell Transplantation on Dental Development.

To investigate dental development in patients treated with a hematopoietic stem cell transplantation (HSCT), 42 children and young adults who were under 12 years old at time of HSCT were examined for dental agenesis, microdontia, and root-to-crown ratio. Conditioning regimens were total body irradiation (TBI) based in 12 patients, busulfan based in 21 patients, and 9 patients had other chemotherapeutic agents. Sixteen patients were <3 years old, 9 patients were 3 to 6 years old, and 17 patients were 6 to 12 years old at HSCT. Prevalence of agenesis and microdontia of at least 1 permanent tooth were, respectively, 51.3% and 46.2% in the study population, and 76.3% had an aberrant root-to-crown ratio. All these results were highly different from the prevalence in the healthy population. Patients treated before the age of 3 years had more microdontia (76.9%) and agenesis (92.3%) compared with patients treated at an older age. In the subgroup of patients treated after 6 years, there was more microdontia when treated with busulfan (50%) compared with treatment with TBI (0%) (P = .044). Patients treated with HSCT had many disturbances in dental development. Age at HSCT and possibly also the conditioning regimen used had an effect on their type and prevalence. Dental follow-up should be incorporated in the multidisciplinary follow-up program of these patients.

The Efficacy and Late Toxicities of Computed Tomography-based Brachytherapy with Intracavitary and Interstitial Technique in Advanced Cervical Cancer.

Purpose: To report the efficacy and late side effects(LSEs) of CT-based image-guided brachytherapy for the treatment of cervical cancer. Materials: Between 2008 and 2014, 100 patients with FIGO stage IIB-IVA cervical carcinoma were analyzed. The patients received pelvic irradiation (45-50 Gy in 25 fractions) with concurrent chemotherapy, whereas the mean prescribed EBRT dose, including initial and boost doses to positive lymph nodes, ranged from 54 to 64 Gy. Afterwards, intracavitary(IC) or combined intracavitary/interstitial(IC/IS) brachytherapy was performed using a CT-based procedure with prescribed doses of 6 or 8 Gy in 3-7 fractions. Results: The median follow-up time was 46 months. The 5-year local control, distant metastasis-free survival, and overall survival rates were 88.9%, 81.8%, 77.9%, respectively. IC/IS brachytherapy improved the HR-CTV D90 compared with IC (p<0.01). Seven patients (7.0%) had grade 2 bladder LSEs and none had grade 3/4 bladder LSEs. There was no significant relationship between bladder LSEs and the dose-volume histogram (p>0.05 for all). Thirty-seven patients (37%) had grade 2 rectal LSEs, 3(3%) had grade 3 rectal LSE. The rectum D1cc, D2cc, and D5cc values were significantly higher in patients with grades 2/3 rectal toxicity than in those with grades 0/1 (p<0.05 for all). There was no grade 2 and above small bowel LSEs. Conclusions: CT-based brachytherapy planning can achieve excellent local control with acceptable morbidity. HR-CTV D90 can increase in the IC/IS group compared with the IC group. The D1cc, D2cc, and D5cc all showed excellent predictive values for rectal LSEs.

Late rectal toxicity determined by dose-volume parameters in computed tomography-based brachytherapy for locally advanced cervical cancer.

The aim of this study was to observe the relationship between dose-volume histogram (DVH) parameters and rectal late side effects (LSE) in computed tomography (CT)-based brachytherapy (BT) for patients with locally advanced cervical cancer. In total, 144 cervical cancer patients received external beam radiotherapy and CT-based BT. The data from 111 survival cases with pelvic local control (LC) were used to analyze the relationship between DVH parameters and rectal LSE. The total doses, manifesting 2, 1, and 0.1 cm(3) (D2cc , D1cc , and D0.1cc ) of the rectum, and D90 for high-risk clinical target volume (HR CTV) were computed and normalized to 2 Gy fractions (EQD2) using a linear-quadratic model. The rectal LSE were evaluated by the late effects in normal tissues-subjective, objective, management, and analytic (LENT-SOMA) scale. A dose-response relationship was evaluated by probit analyses. For all patients, the total rate of rectal LSE was 56%, and the rate of ≥Grade 2 LSE was 27.4%. For the 111 survival cases with pelvic LC, the total mean for D2cc was 71.23 ± 5.54 Gy for the rectum, and the D2cc , D1cc , and D0.1cc values for Grades 2 and 3 were higher than those for Grades 0 and 1. In addition, the number of complications increased, and the complications became more severe as the dose increased, with a dose of 73.5 Gy resulting in a 10% probability of ≥Grade 3 LSE. In conclusion, DVH parameters could predict the incidence and grades of rectal LSE in CT-based BT. D2cc showed an excellent predictive value, and 73.5 Gy for D2cc of the rectum might be considered as an alternative dose limit.

Late radiation side effects, cosmetic outcomes and pain in breast cancer patients after breast-conserving surgery and three-dimensional conformal radiotherapy : Risk-modifying factors.

BACKGROUND AND PURPOSE: The purpose of this work was to identify parameters influencing the risk of late radiation side effects, fair or poor cosmetic outcomes (COs) and pain in breast cancer patients after breast-conserving therapy (BCT) and three-dimensional conformal radiotherapy (3D-CRT). PATIENTS AND METHODS: Between 2006 and 2013, 159 patients were treated at the Hannover Medical School. Physician-rated toxicity according to the LENT-SOMA criteria, CO and pain were assessed by multivariate analysis. RESULTS: LENT-SOMA grade 1-4 toxicity was observed as follows: fibrosis 10.7 %, telangiectasia 1.2 %, arm oedema 8.8 % and breast oedema 5.0 %. In addition, 15.1 % of patients reported moderate or severe breast pain, and 21.4 % complained about moderate or severe pain in the arm or shoulder. In multivariate analysis, axillary clearing (AC) was significantly associated with lymphoedema of the arm [odds ratio (OR) 4.37, p = 0.011, 95 % confidence interval (CI) 1.4-13.58]. Breast oedema was also highly associated with AC (OR 10.59, p = 0.004, 95 % CI 2.1-53.36), a ptosis grade 2/3 or pseudoptosis and a bra size ≥ cup C (OR 5.34, p = 0.029, 95 % CI 1.2-24.12). A ptosis grade 2/3 or pseudoptosis and a bra size ≥ cup C were the parameters significantly associated with an unfavourable CO (OR 3.19, p = 0.019, 95 % CI 1.2-8.4). Concerning chronic breast pain, we found a trend related to the prescribed radiation dose including boost (OR 1.077, p = 0.060, 95 % CI 0.997-1.164). Chronic shoulder or arm pain was statistically significantly associated with lymphoedema of the arm (OR 3.9, p = 0.027, 95 % CI 1.17-13.5). CONCLUSION: Chronic arm and breast oedema were significantly influenced by the extent of surgery (AC). Ptotic and large breasts were significantly associated with unfavourable COs and chronic breast oedema. Late toxicities exclusive breast pain were not associated with radiotherapy parameters.

Small but significant excess mortality compared with the general population for long-term survivors of breast cancer in the Netherlands.

BACKGROUND: Coinciding with the relatively good and improving prognosis for patients with stage I-III breast cancer, late recurrences, new primary tumours and late side-effects of treatment may occur. We gained insight into prognosis for long-term breast cancer survivors. PATIENTS AND METHODS: Data on all 205 827 females aged 15-89 diagnosed with stage I-III breast cancer during 1989-2008 were derived from the Netherlands Cancer Registry. Conditional 5-year relative survival was calculated for every subsequent year from diagnosis up to 15 years. RESULTS: For stage I, conditional 5-year relative survival remained ~95% up to 15 years after diagnosis (a stable 5-year excess mortality rate of 5%). For stage II, excess mortality remained 10% for those aged 15-44 or 45-59 and 15% for those aged 60-74. For stage III, excess mortality decreased from 35% at diagnosis to 10% at 15 years for those aged 15-44 or 45-59, and from ~40% to 30% for those aged ≥60. CONCLUSIONS: Patients with stage I or II breast cancer had a (very) good long-term prognosis, albeit exhibiting a small but significant excess mortality at least up to 15 years after diagnosis. Improvements albeit from a lower level were mainly seen for patients who had been diagnosed with stage III disease. Caregivers can use this information to better inform (especially disease-free) cancer survivors about their actual prognosis.

Reirradiation of relapsed brain tumors in children.

AIM: The aim of this study was to evaluate toxicity and response to fractionated reirradiation (FR) of relapsed primary brain tumors in children. BACKGROUND: The treatment options for recurrent brain tumors in children previously irradiated are limited. Reirradiation is performed with fear due to the cumulative late CNS toxicity and the lack of a significant chance of cure. MATERIALS AND METHODS: Between 2008 and 2009, eight children with a median age of 14.5 years with a diagnosis of a recurrent brain tumor underwent reirradiation. Initially, all patients were treated with surgery, chemotherapy and radiotherapy. The median time to the first recurrence after the initial treatment was 19.5 months. Intervals between radiotherapy courses were in the range of 5-51 mos. All retreatments were carried out with 3D image-based conformal methods. The total prescription dose was 40 Gy in a fraction of 5 × 2 Gy/week. The total cumulative dose ranged from 65 to 95 Gy (median: 75 Gy). The median cumulative biologically effective dose was 144 Gy (range: 126-181 Gy). RESULTS: The median overall survival and progression free survival measured from the beginning of reirradiation was 17.5 and 6.5 months, respectively. During the first evaluation, four patients showed a complete or partial response, two did not respond radiologically. Two children were progressive at the time of reirradiation. Among children with progression that occurred during the first year after reirradiation, only two progressed in the treatment area. The repeated irradiation was well tolerated by all patients. No late complications have been observed. CONCLUSION: In the absence of other treatment possibilities, the fractionated reirradiation with highly conformal three-dimensional planning could be a therapeutic choice in case of recurrent brain tumors in children. The control of craniospinal dissemination remains to be the main problem.