Incidence Of Late Effects Research Articles

Multimorbidity Among Adolescent and Young Adult Thyroid Cancer Survivors: A Report From the AYA VOICE Study

Background: Thyroid cancer is one of the most common cancers in adolescents and young adults (AYA, 15 to 39), with excellent 5-year survival of 98%. However, treatments for thyroid cancer such as radioactive iodine and thyroid hormone suppression may increase the risk for multiple late effects (LE). We investigated the incidence of severe LE that cluster in AYA thyroid cancer survivors in a large population-based cohort. Methods: We used California Cancer Registry records to identify AYAs diagnosed with first primary thyroid cancer during 2006–2018 linked to statewide hospitalization, ambulatory surgery, and emergency department data. Cohort entry began 2 years from diagnosis. Severe LE included cardiovascular, respiratory, endocrine, renal, and liver diseases, and second cancers. Cumulative incidence of each LE, accounting for the competing risk of death, was calculated. Latent class analysis (LCA) identified clustering of LE overall and in <5 and ≥5-year survivors. The number of LE classes was identified by selecting models with the lowest likelihood-ratio G2 statistic, Akaike's Information Criterion, and Bayesian Information Criterion. Probabilities of each LE are presented in each class. Results: Of 12,224 survivors, 83% were female, 34% were Hispanic, and 62% aged 30–39 years at diagnosis. Mean follow-up time was 7.9 years. Five-year cumulative incidence was highest for endocrine (27.9%, 95% CI 27.0–28.8), respiratory (5.1%, 95% CI 4.6–5.5), and cardiovascular (2.1%, 95% CI 1.8–2.4) diseases. The LCA model identified 3 classes: 78.6% were ‘healthy survivors’ with a low probability of any LE, 19.8% experienced a high probability of endocrine (95%) conditions, and the remaining 1.6% were ‘multimorbidity survivors,’ experiencing a high probability of all LEs, particularly endocrine (94%), cardiovascular (61%), renal (55%), and respiratory (46%) conditions, followed by liver disease (25%) and second cancers (9%). No differences were found in the LCA classes among <5 and ≥5-year survivors. Conclusion: While most survivors of AYA thyroid cancer have few severe LEs, >20% have a high probability of endocrine conditions or multimorbidities. Multidisciplinary survivorship care may be vital to supporting thyroid cancer survivors experiencing multiple LEs.

Abstract IA28: Disparities in late effects incidence among adolescent and young survivors of lymphoma

Abstract IA28: Disparities in late effects incidence among adolescent and young survivors of lymphoma

Lifelong disease burden of chemotherapy in Hodgkin lymphoma (HL): A simulation study from the St. Jude Lifetime (SJLIFE) Cohort and HL International Study for Individual Care (HoLISTIC).

12068 Background: Current emphasis for childhood and young adults with HL is to maintain high cure rates while concurrently identifying regimens to reduce excess long-term mortality/morbidity. Thus, understanding the late effects (LE) of contemporary clinical trials (CCT) for HL is critical. Methods: We used simulation to estimate the projected life expectancy (LExp), quality adjusted life-expectancy (QALE) & cause of death (COD) in a large cohort of HL CCT patients (pts) in the recently established HoLISTIC consortium by linking long-term risk models from the SJLIFE cohort. Individual patient data (IPD) on bleomycin, alkylating agents and anthracycline were extracted & harmonized for 982 HL pts in 5 prospective CCT (mean diagnosis age 19y, range 3-30y; 51% male; all treated with chemotherapy only; progression-free survival [PFS] >5y) in the HoLISTIC database. LExp, QALE & COD were projected using a previously developed microsimulation model (Bhakta, Blood [Supplement], 2019) that incorporated mortality & incidence of LEs by diagnosis age, sex, race, treatment exposures & attained age estimated from 5,522 adult 10-y survivors of childhood cancers in the SJLIFE cohort (56% male; mean age at last follow-up 35y, range 19-68). Microsimulation was applied to 10,000 randomly selected survivors of HL CCT cohort, from 10y after HL diagnosis until death to project the LExp, QALE & COD. Results: Assuming 10-y PFS, LExp and QALEs projected for the HL CCT cohort using adjusted US general population rates linked with the SJLIFE microsimulation model, COD and trial-specific exposures are shown in the Table. Conclusions: A novel lifetime simulation approach was used to project LExp, QALE & COD by linking together IPD from CCTs with the long-term risk model of the SJLIFE survivorship cohort. Despite differences in PFS, reflecting in part the variation in risk/stage status, the projected long-term outcomes were similar. Our approach highlights a new opportunity to inform future clinical trial design and aid provider & patient decision-making. [Table: see text]

Barriers to caring for survivors of childhood cancer: Primary care providers’ and oncologists’ perspectives.

e19194 Background: Advances in treatment have resulted in a growing population of childhood cancer survivors. As most survivors will develop at least one late effect from treatment, it is important to continue to monitor their health. The incidence of late effects increases with age and often are not clinically apparent until decades after cancer treatment. The Institute of Medicine has recommended models of care delivery that include collaboration between oncologists and primary care physicians (PCP). Thus, we explored PCP and pediatric oncologists’ perceptions and experiences with survivors of childhood cancer in primary care. Methods: Recruitment of primary care physicians occurred utilizing the state Board of Medicine listings. A link and a paper copy of the survey were supplied via mail to approximately 3,000 pediatricians. Pediatric oncologists from a large Midwestern hospital completed the survey via email. Results: A total of 197 participants (19 oncologists/ 178 PCPs) completed the survey. The response rate was 95% for oncologists and 6% for PCPs. Although most PCPs (76%, n=134) had cared for a childhood cancer survivor, some respondents (16%, n=8) reported an unwillingness to care for a survivor. Using a ten-point scale, PCPs mean comfort level in caring for survivors of pediatric cancer was 5.78 ( SD= 2.37). PCPs identified the following barriers: limited knowledge of late effects (64%; n=114), lack of communication with oncologist (47%; n=83), and comfort level (38%; n=67). Nearly all oncologists (86%, n=19) reported referring patients to PCPs. Oncologists typically (83%, n=15) referred patients within the first year after treatment. Overall, oncologists were comfortable referring survivors to a PCP ( M=7.5; SD=1.97) and over half were satisfied with the PCP’s care of survivors (57%, n=12). Years in practice and sex of the oncologist were unrelated to comfort level referring to PCP. Conclusions: Barriers faced by PCPs in caring for survivors illustrate a need for increased education and communication between PCPs and oncologists. Attention to these concerns may improve follow-up care and comfort in the referral process.

Documentation and incidence of late effects and screening recommendations for adolescent and young adult head and neck cancer survivors treated with radiotherapy.

A retrospective review of adolescent and young adult (AYA) head and neck cancer (HNC) patients treated with radiation therapy (RT) at British Columbia Cancer was performed to determine the incidence of late toxicities, the documented late side effects discussed and the screening recommendations provided at the time of transfer of care to primary care providers (PCPs). Charts (n = 162) were reviewed for all patients 15 to 35years at diagnosis with HNC treated with RT from 1960 to 2010 who survived > 5years after diagnosis. A discussion regarding the risk of long-term side effects was documented in the initial consultation for 85% of patients. The majority of patients (78%) developed > 1 documented late effect. The most common were xerostomia (44%), skin changes (28%), neck fibrosis (22%), nasal crusting (16%), epistaxis (16%), and dental decay (14%). In all, 20% were currently followed or were followed until they died. Of the 80% transferred to their PCP, 14% had a formal discharge summary. For those discharged from British Columbia Cancer, documented recommendations included regular dental care (34%) and screening for hypothyroidism (5%) and second malignancy (4%). The majority of AYA HNC patients treated with RT developed late side effects, and most PCPs were not sent a discharge summary outlining screening recommendations for delayed late effects. AYA HNC survivors treated with RT are at high risk for late effects and would benefit from a survivorship care plan outlining these risks and screening recommendations.

Exploring the spectrum of late effects following radical orchidectomy for stage I testicular seminoma: a systematic review of the literature.

Testicular seminomas occur in young men and are highly curable. Toxicities following treatment for men with extensive stage II-III seminomas may cause long-term morbidities. However, it is not clear whether the risk of late effects also increases following surgery for testis-confined seminoma. In this systematic review, we examined the available literature regarding the incidence of late effects in our target population of patients with stage I seminoma treated with orchidectomy alone. Publications were identified through an electronic literature search using the MEDLINE, EMBASE and PsychInfo databases, identifying cohorts treated for stage I seminoma. Data on late effects were collected and classified as physical or psychological. Six hundred and four articles were screened to identify 100 studies. In the target population, available evidence suggests no increased risk of cardiovascular disease, metabolic syndrome, or renal dysfunction compared to the general population. Sperm counts were initially lower than an age-matched cohort; however, counts normalised when re-assessed 5years later. Data were not specifically reported for the target population regarding bone health, second malignancy, hypogonadism, fertility and all psychological domains. Heterogeneity of study design and reporting methods contributed to uncertainty regarding the true incidence and clinical significance of late effects. The curability of stage I seminoma and the wide range of potential late effects of treatment suggest the need for long-term monitoring alongside standard cancer surveillance. Important data are needed on the prevalence of late effects, specifically related to testicular cancer survivors undergoing surveillance following orchidectomy. Awareness and screening for relevant late effects may prevent further morbidity in men treated for stage I seminoma.

Combined therapy in children and adolescents with classical Hodgkin's lymphoma: A report from the SFCE on MDH-03 national guidelines

ABSTRACTHodgkin's lymphoma (HL) in children and adolescents is highly curable, but children are at risk of long-term toxicity. The MDH-03 guidelines were established in order to decrease the burden of treatment in good-responder patients, and this report should be considered a step toward further optimization of treatment within large collaborative trials. We report the therapy and long-term outcomes of 417 children and adolescents treated according to the national guidelines, which were applied between 2003 and 2007 in France. The patients were stratified into three groups according to disease extension. Chemotherapy consisted of four cycles of VBVP (vinblastine, bleomycin, VP16, prednisone) in localized stages (G1/95 pts/23%), four cycles of COPP/ABV (cyclophosphamide, vincristine, procarbazine, prednisone, adriamycin, bleomycin, vinblastine) cycles in intermediate stages (G2/184 pts/44%) and three cycles of OPPA (vincristine, procarbazine, prednisone, adriamycin) plus three cycles of COPP in advanced stages (G3/138 pts/33%). Radiation therapy of the involved field was given to 97% of the patients, with the dose limited to 20 Gy in good responders (88%). With a median follow-up of 6.6 years, the 5-year event-free survival (EFS) and overall survival (OS) were 86.7% (83.1–89.7%) and 97% (94.5–98.1%), respectively. EFS and OS for G1, G2, and G3 were 98% and 100%, 81% and 97%, and 87% and 95%, respectively. Low-risk patients treated without alkylating agents and anthracycline had excellent outcomes and a low expected incidence of late effects. Intensification with a third OPPA cycle in high-risk group patients, including stage IV patients, allowed for very good outcomes, without increased toxicity.

Incidence of late effects in long-term childhood cancer survivors.

e22009Background: As therapies for children with cancer have improved, the need for greater attention to adult survivors is becoming more recognized. Our study examined the rates of physician-deter...

Abstract P2-11-12: Proactive approach to risk reduction and early detection of breast cancer related lymphedema

Abstract Advances in surgery and post-operative treatment continue to reduce the incidence of late effects of cancer treatment such as lymphedema. Yet, many breast cancer survivors still face considerable post-operative challenges as a result of developing lymphedema. The purpose of this study was to preliminarily evaluate a nursing educational and behavioral program “The Optimal YOU” to enhance lymphedema risk reduction, focusing on preventing inflammation-infection, promoting lymph drainage, and maintaining optimal Body Mass Index (BMI) as well as preoperative and subsequent follow-up assessment of limb volume changes and symptoms. A quasi-experimental design with repeated-measures was used. The Study outcomes included lymph volume changes by infra-red perometer, lymphedema-related symptoms, and BMI by Bioimpedance at pre-operative baseline, post-operative, 6-month, and 12-month follow-up. A total of 147 patients were recruited and received the program, 141 patients completed the study (4% attrition rate). Majority (over 90%) of patients maintained preoperative limb volume and improved their symptom experience at 12-month follow-up. During the study period, only 7 patients (5%) had measurable lymphedema. At 12-month follow-up, among the 7 patients who developed measurable lymphedema, 2 patients' limb volume returned to pre-operative level without compression therapy only by maintaining exercises of The Optimal YOU to promote daily lymph flow. About 80% of patients maintained or improved their preoperative BMI. Implementation of this nursing educational and behavioral intervention is effective to enhance lymphedema risk reduction and early detection. Findings of the study provided evidence to support the emerging policy change in lymphedema care, shifting treatment-focus care to proactive risk reduction. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-11-12.

Proactive approach to risk reduction and early detection of breast cancer-related lymphedema.

95 Background: Advances in surgery and post-operative treatment continue to reduce the incidence of late effects of cancer treatment such as lymphedema. Yet, many breast cancer survivors still face considerable post-operative challenges as a result of developing lymphedema. The purpose of this study was to preliminarily evaluate an educational and behavioral program “The Optimal YOU” to enhance lymphedema risk reduction among patients with breast cancer. The intervention focuses on preventing inflammation-infection, promoting lymph drainage, and maintaining optimal BMI as well as preoperative and subsequent follow-up assessment of limb volume changes and symptoms. Methods: A quasi-experimental design with repeated-measures was used to assess outcomes of The Optimal YOU program at pre-operative baseline, post-operative, 6-month, and 12-month follow-up. A total of 147 patients newly diagnosed with breast cancer were recruited and received the program. The program outcome data include lymph volume changes by infra-red perometer-S350, lymphedema-related symptoms by Lymphedema Symptom Experience Index, and body mass index (BMI) by Bioimpedance DF50. Results: Among the 147 patients, 141 patients completed the study (4% attrition rate). Majority (94%) of patients maintained preoperative limb volume and improved their symptom experience at 12-month follow-up. During the 12-month study period, only five patients (6%) developed lymphedema and were referred for lymphedema treatment. At 12-month follow-up, among the five patients who developed measurable lymphedema, two patients’ limb volume returned to pre-operative level without compression therapy only by maintaining exercises of The Optimal YOU to promote daily lymph flow. About 80% of patients maintained or improved their preoperative BMI. Conclusions: The study shows that proactive approach to implementing The Optimal YOU program is effective to risk reduction and early detection of breast cancer-related lymphedema by focusing on preventing inflammation-infection, promoting lymph drainage, and maintaining optimal BMI.

Longitudinal changes in health care utilization by adult survivors of childhood cancer in the Childhood Cancer Survivor Study (CCSS).

6030 Background: The incidence of late effects increases as childhood cancer survivors age. Survivors require lifelong care focused on the risks arising from prior cancer therapy (survivor-focused care). Methods: We assessed longitudinal changes in health care utilization in adult survivors of childhood cancer participating in the CCSS. Utilization at baseline and most recent follow-up was classified into one of three mutually exclusive hierarchical categories: no health care, general medical care, or survivor-focused care. Relative risk (RR) and 95% confidence intervals (CI) were calculated for predictors of reduction in care over time from survivor-focused to general or no care. Multivariable models, adjusted for key treatment exposures, were created to assess the risk factors for reductions in level of care over time. Results: Among 8591 eligible survivors, mean age at last follow-up was 35.1 years (SD=7.8) with a mean of 11.6 years (SD=2.2) since baseline. Of 3993 (46%) survivors who reported survivor-focused care at baseline, 2383 (59.7%) reported a lower level of care at follow-up. Among 4598 (54%) not receiving survivor-focused care at baseline, 915 (20%) reported survivor-focused care at follow-up. Baseline predictors of a decreased level of care were no health insurance (RR=1.5, 95% CI 1.2-1.9), male sex (RR=1.4, 95% CI 1.2-1.6), being 10-19 years from diagnosis compared with 20+ years (RR=1.4, 95% CI 1.1-1.7). In contrast, factors associated with a maintenance in survivor-focused care were Canadian residency compared to U.S. residency with insurance (RR=0.7, 95% CI 0.6-0.9), unemployment (RR=0.8, 95% CI 0.7-0.9), physical limitations (RR=0.7, 95% CI 0.6-0.9), cancer-related pain (RR=0.7, 95% CI 0.5-0.8), poor emotional health (RR=0.7, 95% CI 0.5-0.9), having mild-moderate (RR=0.5, 95% CI 0.4-0.6) or severe-disabling chronic health condition (RR=0.6, 95% CI 0.5-0.7). Conclusions: Less than a third of adult survivors of childhood cancer report survivor-focused care. Rates decrease over time. Targeted interventions to maximize survivor-focused care in at-risk survivors should be tested so preventive and risk-reducing opportunities are not lost.

Clinical outcome of three fractionation schedules of preoperative radiotherapy for rectal cancer

Summary Aim To evaluate the effectiveness and normal tissue reactions of three fractionation schedules of preoperative radiotherapy for locally advanced rectal cancer. Materials and Methods Between 1996 and 2002, 168 patients with locally advanced rectal cancer were treated as follows: 53 patients received 25 Gy in 5 Gy per fraction (group A), 45 received 30 Gy in 3.0 Gy per fraction (group B), and 70 were treated with accelerated hyperfractionation: 42 Gy, 1.5 Gy per fraction, given twice a day with an inter-fraction interval of 6 hours (group C). The clinical characteristics of the groups were comparable. The patients did not receive concurrent chemotherapy. A Cox proportional hazard regression model was used to analyze the factors which may influence loco-regional tumour control (LRC) and overall survival (OS). Results The following variables significantly influenced LRC: fractionation scheme (5-year LRC 80%, 69%, and 90% in groups A, B, C respectively, p=0.016), haemoglobin concentration before radiotherapy (p= 0.012) and postoperative chemotherapy (p=0.01). Age, sex, stage of disease, location of tumour (distance of the tumour from the anal verge) and performance status did not appear significant for LRC. The overall 5-year OS was 64%, 59% and 74% in groups A, B, C respectively (p=0.056). The OS was significantly influenced by postoperative pathological stage (p=0.006), tumour location (p= 0.015) and postoperative chemotherapy (p=0.047). The most frequent acute radiation reaction was mild/severe diarrhoea, which appeared in 5%, 21.6% and 65.5% of the patients from groups A-C respectively. The median wound healing time in those who underwent abdominoperineal resections was 6, 6 and 4 weeks. Other reactions appeared less relevant. There was no significant difference in the incidence of late effects among the three treatment groups. Conclusion While due to the non-randomized character of the study the conclusions should be regarded as hypothesis-generating only, the analysis has shown an acceptable local effectiveness and tolerance of schedules A and C, and disappointing effectiveness of schedule B. The present study thus supports the data which suggest that the clinical effect of preoperative radiotherapy for rectal cancer is influenced not only by total radiation dose but also by overall radiation treatment time and dose per fraction.

Acute and late effects of radical radiotherapy in elderly head and neck cancer patients

16515 Background: To evaluate the difference between acute and late effects of radical radiotherapy in elderly(above 60 years,Group A) head and neck cancer patients with young patients (below 50 years of age, Group B). Methods: The study was conducted on histologically proven head and neck cancer patients receiving radical radiotherapy (RT),49 patients were in group A and 40 in group B.The acute and late radiation morbidity was assessed using RTOG (phases I,II,&III- Pre RT, During RT & 1 month post RT respectively) and LENT-SOMA scoring systems (phases IV &V-3 & 6 months post RT). Results: In phase II, grade I dermatitis was commonly seen (83.7% in group A,72.5% in group B) and grade II dermatitis was 12.2 % vs 25% of patients.The difference in distribution over age was not significant (p= 0.12 & 0.18 in phase II and III).There was no significant difference in the incidence of late effects between two groups (p=0.91 in phase IV and p=0.99 in phase V).Grade II mucositits was seen in majority of patients in both groups,71.4% vs 72.5% in phase II.The late mucosal changes with worrisome subjective (pain) experiences were observed in 69.4% vs 75% of patients in group A and B, respectively.The difference in distribution over the age was significant (p<0.051) only in phase II.Dryness of mouth was the most common acute and late sequel of RT.The acute salivary gland morbidity was mostly moderate to complete dryness (grade II),seen in phases II and III in 24.5% & 73.5% of patients but the late sequel was seen in 83.37% of patients in group A and 85% in group B and the difference in late effects in both groups was statistically significant except in phase V (p= 0.02). Moderate dysphagia of grade II morbidity was seen in 75.5% vs. 65% in phase II. Grade III dysphagia was seen only 5 patients in group A and one in group B. In phase IV,66.7% patients in group A,72.5% in group B had persistent difficulty in swallowing. Conclusions: Grade I and II mucositis and dermatitis during the course of treatment led to increased morbidity, decreased nutritional intake and pain. Xerostomia is the most common and inevitable acute and late squeal of radical radiotherapy to head and neck cancer region resulting in difficulty in mastication and swallowing. There was no difference in the occurrence of acute and late effects between younger and elderly patients. No significant financial relationships to disclose.

Late Effects and Quality of Life of Survivors of Childhood Hematologic Malignancies Treated Mainly during 80's in Japanese Group Study.

Persons who were treated mainly in 80's were reviewed and assessed for the present status including late effects, school, social life, marital state.Questionaire was sent to individual institutions and answers were returned from physicians or survivors themselves.From 1881 to 1994, there were five clinical protocols in ALL, four in AML, and three in NHL. Registered and surviving numbers were 1,023 and 642 in ALL, 309 and 164 in AML, 200 and 166 in NHL. Of surviving numbers, responded number was 521 in ALL, 142 in AML, 103 in NHL. Of these 1,262 survivors, 128 persons have proven to have some kinds of late effects. Mean age of survivors was 6.7 at the onset of disease and 18.6 at the time of this survey. Questionair was as followings; diagnosis, gender, age, presence or absence of late effects, detail of late effects, and present status. As a result, 128 survivors (male/female; 78/50, ALL; 75, AML; 30, NHL; 23) have 169 items of late effects. The overall incidence of late effects was 13% in ALL and 20% in AML and NHL. There was no difference of incidence between each treatment protocols in ALL.Additionally, 10 persons died with late effects. Of those, the cause of death was as followings; leukoencephalopathy; 3, cardiac toxicity 3, of them, one boy was in remission after completion of chemotherapy and died during running, relapse of primary disease; 1, secondary cancer; 1, measles; one who was in remission at the time of infection, ARDS; one who received stem cell transplantation. The late effects were classified as following categories (sALL/hALL/AML/NHL); hepatic 30(14/7/6/3), cardiac 7 (3/2/0/2), central nervous system 33 (13/6/6/8), short stature 29 (14/6/5/4), gonad 16 (3/4/9/0), thyroid 4 (1/1/2/0), renal 8 (3/1/2/2), pulmonary 6 (1/2/2/1), cGVHD 4 (1/2/1/0), secondary cancer 6 (4/0/0/2), others 26 (5/3/11/7).The number of each category of late effects was so small, that decreasing tendency was not apparent with time course of this studying period except hepatic disorder, which is related to post-transfusion hepatitis C. CNS disorders include leukoencephalopathy, mental retardation, epilepsy, and visual disturbances. More than one half of short stature was found in the standard risk ALL. Most of gonad dysfunction, persistent alopecia, pulmonary and renal disorders were related to stem cell transplantation. Psychological or mental disturbance, which are related school troubles, was also observed. Second cancer found in six persons. Primary diagnosis of secondary cancer was ALL in 4 and NHL in 2.For these persons who have late effects, present state of individual life was evaluated and classified into four categories; (1) usual life without handicapped and medical service, (2) no handicapped, but necessary medical service, (3) handicapped, but unnecessary medical service, (4) handicapped, and necessary medical service. Each category was found in any primary disease or type of treatment.Discussion: The several major late effects of survivors will not decrease in near future, considering the number of survivors is increasing for these decades. Novel system for survivors should be build up as to make their lives healthier.

Dose-volume histogram analysis does not completely predict the incidence of late effects of radiation in prostate cancer

Purpose/Objective: To determine whether dose alone is sufficient to predict morbidity outcomes in the radiation treatment of cancer of the prostate. Toward this end, factors other than the dose distribution must be included in the analysis simultaneously with the dose distribution. The factors examined include radiation dose distribution in the form of the dose-volume histogram (DVH), intercurrent diseases, and hormonal therapy.

Dose-volume histogram analysis does not completely predict the incidence of late effects of radiation in prostate cancer

Dose-volume histogram analysis does not completely predict the incidence of late effects of radiation in prostate cancer

Quantification of late complications after radiation therapy

Abstract Background : An increasing number of patients survive cancer after having received radiation therapy. Therefore, the occurrence of late normal tissue complications among long-term survivors is of particular concern. Methods : Sixty-three patients treated by radical surgery and irradiation for rectal carcinoma were subjected to an unconventional sandwich therapy. Preoperative irradiation was given in four fractions of 5 Gy each applied within 2 or 3 days; postoperative irradiation consisted mostly of 15×2 Gy (range, 20–40 Gy). A considerable proportion of these patients developed severe late complications (Radiother Oncol 53 (1999) 177). The data allowed a detailed analysis of complication kinetics, leading to a new model which was tested using data from the literature. Results : Data on late complications were obtained for eight different organs with a follow-up of up to 10 years. For the various organs, the percentage of patients being free from late complications, plotted as a function of time after start of radiation therapy, was adequately described by exponential regression. From the fit, the parameter p a was obtained, which is the percentage of patients at risk in a given year of developing a complication in a given organ during that year. The rate p a remained about constant with time. Following sandwich therapy, the annual incidence of complications in the bladder, ileum, lymphatic and soft tissue, and ureters was about the same ( p a =10–14%/year), whereas complications in bone or dermis occurred at lower rates (4.7 or 7.5%/year, respectively). Discussion : Numerous data sets collected from published reports were analyzed in the same way. Many of the data sets studied were from patients in a series where there was a high incidence of late effects. Three types of kinetics for the occurrence of late effects after radiotherapy were identified: Type 1, purely exponential kinetics; Type 2, exponential kinetics, the slope of which decreased exponentially with time; Type 3, curves composed of two components, a fast initial decline followed by an exponential decrease. For each kind of kinetics, provided that the dose distribution is not too heterogeneous, the incidence of late effects appears to occur at exponential or approximately exponential kinetics, even many years after treatment. This implies that a random process might be involved in the occurrence of late radiation sequelae. Conclusions : There might be a lifelong risk of developing late complications, of which patients and clinicians should be aware. It appears worthwhile to try to identify, in follow-up examinations of patients after radiation therapy, what kind of processes might be involved in triggering subclinical residual injury to develop into a clinically manifest late effect.

Conformal Radiotherapy and Intensity-modulated Radiotherapy: Clinical Data

Conformal radiotherapy (CRT) is based on three hypotheses: (i) a higher rate of local control can improve the survival rate; (ii) dose escalation can increase tumor control; and (iii) CRT allows the delivery of higher doses by decreasing the incidence of late effects. These postulates are now supported by several data. Three-dimensional conformal radiotherapy (3D-CRT) has markedly progressed since its introduction two decades ago. However, there are situations for which 3D-CRT cannot produce a satisfactory treatment plan because of complex target volume shapes or the close proximity of sensitive normal tissues. This is why intensity-modulated radiation therapy (IMRT) was introduced. Its aim is to overcome the limitations of 3D-CRT by adding modulators of beam intensity to beam shaping. IMRT can achieve nearly any dose distribution; however, the role of the planner remains crucial. CRT has been investigated mainly for prostate cancers and head and neck cancers. By and large, the clinical data, although still limited, seem to confirm the advantages of this type of radiotherapy. Dose escalation in prostate cancers improves the local control rate without increasing late effects and for this cancer site IMRT appears to be a significant advance over conventional 3D-CRT. In head and neck cancers the clinical data are still scarce but encouraging. CRT should be investigated in breast cancers with the aim of reducing the incidence of late effects. The available data underline the great potential for major progress in 3D-CRT and IMRT. The techniques are still costly and time consuming, nevertheless they merit investigation since their cost should decrease. Efforts should be concentrated on the specification of robust optimization criteria, taking into account clinical and radiobiological data.

A linear quadratic analysis of gynaecological brachytherapy

Four hundred and fourteen patients were treated by radical radiotherapy alone for cervical carcinoma at the Western Infirmary and the Royal Beatson Memorial Hospital between April 1982 and December 1987. All patients received external beam radiotherapy in addition to brachytherapy, using either manually inserted caesium ( n = 107) or the Selectron afterloading machine ( n = 307). Three mean Selectron dose rates were used: 0.91 Gy/h, 1.195 Gy/h and 1.74 Gy/h. During this period of time, the cumulative radiation effect formula was used to calculate an overall brachytherapy dose reduction to compensate for the increase in point ‘A’ dose rate. We have compared the local control rates and the incidence of late effects seen in these patients with theoretical parameters calculated using the linear quadratic (LQ) model. This model predicts a small rise in late effects as the dose rate increases, which is also seen in clinical practice; it also predicts a reduction in local control, partially offset by the addition of external beam radiotherapy, which would be most marked for early stage disease. There was a small fall in local control associated with Selectron treatment, but of a smaller size than predicted by the LQ model.

Dose, time, and fraction size issues for late effects in head and neck cancers

This paper contains a statistical analysis of the dose-time factors influencing late complications in 784 patients with squamous cell carcinomas of the pharynx or larynx treated with external beam irradiation only at the University of Florida. The patients include 560 who received continuous course once-a-day therapy, 116 who received twice-a-day treatment, and 108 who received a once-a-day split course regimen. Both 2 + and 3 + complications were considered. Fifty-six patients developed either of these complications. The factors included in the analysis were site and size of the primary, total dose, fraction size, and treatment time. The linear-quadratic model was used to incorporate fraction size into the analysis. Proportional hazards analysis, which models the time to occurrence of the late complication, was used to quantify the joint influence of the above patient and fractionation variables on the incidence of late effects. The occurrence of the late effects was heterogeneous, with only a weak relationship to the patient and fractionation variables. The influence of the size of the primary was significant, with larger primaries associated with higher complication rates independent of fractionation variables. For oropharynx primary sites there was no significant effect of the fractionation variables. For larynx and hypopharynx, excluding T1–T2 true vocal cord, there was a significant effect of total dose and fraction size. The alpha/beta ratio was estimated to be 7.8 Gy (95% confidence interval, 3.0, ∞). There was no significant effect of overall treatment time. The estimated 2 + complication rate at 1 year from 68 Gy given in 2 Gy fractions in 50 days is 0.1% for T 1–2 vocal cord, 4.1% for T1–T2 supraglottic larynx, 3.8% for T3 supraglottic larynx and vocal cord, 14.9% for T4 supraglottic larynx, 6.7% for T1–T2 tonsil and soft palate, 7.6% for T3–T4 tonsil and soft palate, 7.0% for T1-T2 pyriform sinus and pharyngeal wall, and 13.0% for T3–T4 pyriform sinus and pharyngeal wall.