Severity Of Late Toxicity Research Articles

Long-Term Toxicity and Efficacy of Intensity-Modulated Radiation Therapy in Cervical Cancers: Experience of a Cancer Hospital in Pakistan.

PURPOSETo report the chronic toxicity and disease outcomes attributable to intensity-modulated radiation therapy (IMRT) in patients with cervical cancer.METHODS AND MATERIALSBetween January 2014 and December 2018, a retrospective review of medical records of patients with cervical cancer who received radiation therapy with IMRT was performed. Disease and treatment-related details were documented. Follow-up notes were reviewed, and severity of late toxicities was recorded. Overall survival (OS) and disease-free survival (DFS) at 3 years were estimated.RESULTSA total of 222 patients’ records were reviewed. Mean age was 50.7 years. Median follow-up duration was 33 months (range, 2-70 months). The most common toxicity was vaginal stricture (grade 2, n = 59, 26.6%; grade 3, n = 4, 1.80%), followed by proctitis (grade 2, n = 24; 10.8%; grade 3, n = 7; 3.20%). Seven patients (grade 2, n = 5, 2.3%; grade 3, n = 2; 0.90%) developed cystitis, and only 5 (grade 2; 2.3%) were found to have colitis. None of the patients had grade 4 or grade 5 toxicities. There was a significant difference in late complications in patients with nodal disease or those who underwent prior surgery (P < .05). Three-year OS and DFS rates were 79.7% and 81.9%, respectively. Patients with tumor size > 5 cm and those with pelvic lymph node metastasis had poor survival rates (P < .05).CONCLUSIONIMRT is an effective and well-tolerated technique that should be considered in patients with lymph node disease and in postoperative patients. There is an inverse relationship between tumor size and nodal involvement with respect to OS and DFS.

Late complications of radiation therapy for breast cancer: evolution in techniques and risk over time

Radiation therapy in combination with surgery, chemotherapy, and endocrine therapy as indicated, has led to excellent local and distant control of early stage breast cancers. With the majority of these patients surviving long term, mitigating the probability and severity of late toxicities is vital. Radiation to the breast, with or without additional fields for nodal coverage, has the potential to negatively impact long term cosmetic outcome of the treated breast as well as cause rare, but severe, complications due to incidental dosage to the heart, lungs and contralateral breast. The long-term clinical side-effects of breast radiation have been studied extensively. This review aims to discuss the risk of developing late complications following breast radiation and how modern techniques can be used to diminish these risks.

Analysis of LDR Outcomes in Clinically Localized Prostate Cancer Incorporating a Significant TURP Cohort: A Community Experience

To report the 5 year biochemical relapse free survival (BRFS), overall survival (OS) and long term toxicity outcomes of patients treated with 125Iodine (125I) brachytherapy as monotherapy for clinically localised, low to intermediate risk prostate cancer in the community setting with 3 radiation oncologists and 16 urologists. 371 patients (median age 67 years) with clinically localised prostate cancer were treated from 2004 to 2011 with 125I monotherapy. Median PSA at diagnosis was 5.6 (range 0.6-15.1). T stage was T1 (51%) and T2 (49%) Gleason score was ≤5 (1%); 6 (73%) and 7 (26%). Neoadjuvant hormonal therapy (median 4.5 month course) was used in 84 patients (23%). 102 patients (27%) underwent TURP prior to implant. Patients were evaluated for BRFS, OS and long-term toxicity outcomes. Biochemical relapse was defined by the Phoenix (nadir+2ng/ml) definition. Kaplan-Meier method was used to estimate BRFS and OS, with close-out (censoring) 5 years after implant. Median follow-up time for relapse was 5.2 years with 95% followed up for ≥4 years. 5 year BRFS for the entire cohort was 95%. BRFS by Gleason score classification cohort analysis was 96% and 91% for <6 and 7 respectively. Differences in BRFS between T1 and T2 stages, risk groups (low, low-intermediate, intermediate) and prostate volumes (<30, <40, <50, ≥50 cc) were not significant (p>0.1), probably because the number of relapses was so small. Overall survival was 96% at 5 years, with no deaths from prostate cancer, 7 deaths from other cancers and 7 deaths from other causes. Late grade 2 or 3 toxicities were reported in 10% and 5% of patients respectively with urinary retention in 12% and haematuria in 2%. Urinary incontinence requiring at least 1 pad per day occurred in 3 patients (<1%). Patients with a prior TURP had a greater incidence of late grade 2 or 3 urinary retention (p=0.0011). No patient developed urethral necrosis or recto-prostatic fistula. BRFS and OS results are comparable with published series, as is the incidence and severity of late toxicities. Our results indicate prior TURP is not a contraindication for LDR brachytherapy in cases where implant is technically feasible. However, the risk of subsequent urinary retention is increased.

A retrospective comparison of proton therapy and carbon ion therapy for stage I non-small cell lung cancer

Background and purposeThis retrospective study aimed to compare the clinical outcomes and late toxicities of proton therapy (PT) with those of carbon ion therapy (CIT) for stage I non-small cell lung cancer (NSCLC). Material and methodsA total of 111 patients who underwent particle therapy for stage I NSCLC between April 2003 and December 2009 were enrolled in this study. PT (n=70) and CIT (n=41) were delivered to total doses of 52.8–80GyE in 4–26 fractions and 52.8–70.2GyE in 4–26 fractions, respectively. The median follow-up time was 41months. ResultsDifferences in outcome between the PT and CIT groups regarding 3-year overall survival (72% and 76%, respectively), progression-free survival (44% and 53%, respectively), and local control (81% and 78%, respectively) were not statistically significant. In multivariate analysis, the type of treatment beam did not correlate with overall survival. The severity of late toxicities was comparable between the two groups. ConclusionsClinical results in the PT group were comparable to those in the CIT group. However, this study was a retrospective analysis of a highly heterogeneous population. Consequently, more homogeneous prospective data, large multicentric databases and, ideally, randomized trials are warranted.

Temporal patterns of selected late toxicities in patients treated with brachytherapy or brachytherapy plus external beam radiation for prostate adenocarcinoma

What's known on the subject? and What does the study add? While the frequencies and severity of late toxicities following prostate brachytherapy are well known, less has been published with regard to time to first onset. Several series with limited median follow-up have published time to onset. An extensive analysis of timing to late toxicity following brachytherapy for cervical cancer has also been published. This study is the largest of its kind with the longest median follow-up to capture very late events. It can provide a basis for physician and patient education about when late toxicities can reasonably be expected to occur. The study also shows that a significant amount of erectile dysfunction might be more age related than radiation induced. • To assess the timing of first onset of late rectal bleeding, late haematuria and erectile dysfunction (ED) following brachytherapy with or without external beam radiation therapy (EBRT) for prostate adenocarcinoma. • To identify treatment factors and patient characteristics that affect the time to first onset. • In all, 2046 patients were definitively treated for prostate adenocarcinoma with a full (125) I or (103) Pd implant or a partial (103) Pd implant followed by EBRT with 6 years median follow-up (range 2-17 years). • Patients were selected for an event of Radiation Therapy Oncology Group (RTOG) grade 2 or greater rectal bleeding, ≥RTOG grade 2 haematuria, or a drop in the Mount Sinai Erectile Dysfunction Score from potent to impotent (excluding patients who received androgen deprivation therapy). • Life tables were generated to calculate actuarial incidence rates of toxicity. • Wilcoxon rank sum and Cox regression were utilized to identify treatment factors affecting time to onset. • The incidence rate per 1000 patients for 0-2 years, 2-5 years and 5-10 years following radiation for rectal bleeding is 14.3, 15.9 and 6.5, respectively; for haematuria, 14.0, 8.2 and 1.3, respectively; and for ED, 82.4, 48.2 and 42.2, respectively. • Just 5% of rectal bleeding occurs after 5 years from radiation vs 18% of haematuria cases and 22% of ED. • On multivariate analysis, time to first onset of rectal bleeding was affected by the addition of EBRT only whereas the time to onset of haematuria was affected by the biological effective dose of the radiation and the addition of EBRT. • The only factor on multivariate analysis to affect time to onset of ED was the age of the patient at treatment, independent of radiation dose or technique. • Unique temporality to first onset of selected toxicities was observed in patients after radioactive implant for prostate adenocarcinoma with or without EBRT. • Clinicians and patients should be counselled when to expect late toxicities. • The only factor to affect time to onset of ED is the age of the patient, suggesting possible over-reporting of radiation-induced ED in the light of normal age-related events.

Concomitant Chemoradiotherapy Using Carboplatin, Tegafur-Uracil and Leucovorin for Stage III and IV Head-and-Neck Cancer: Results of GORTEC Phase II Study

Concomitant chemoradiotherapy is the standard treatment of locally advanced, nonresectable, head-and-neck squamous cell carcinoma. However, the optimal chemotherapy regimen is still controversial. The objective of this Phase II study was to evaluate the feasibility and efficacy of a concomitant treatment using tegafur-uracil, leucovorin, carboplatin, and radiotherapy. A total of 77 patients with head-and-neck squamous cell carcinoma Stage III and IVA were enrolled between October 2003 and July 2005. Of the 77 patients, 72 were eligible. They were treated with tegafur-uracil (300 mg/m(2)/d) and leucovorin (75 mg/d) from Days 1 to 19 and from Days 29 to 47 and carboplatin (70 mg/m(2) intravenously for 4 consecutive days), in three cycles every 21 days. Conventional radiotherapy was delivered to a total dose of 70 Gy in 35 fractions. With a mean follow-up of 22.8 months, the 3-year locoregional control, overall survival and disease-free survival actuarial rate was 33.1%, 41.9%, and 27.2%, respectively. The compliance of the treatment was correct. The main acute toxicity was mucositis, with 62% Grade 3-4. Three patients (4.2%) died of acute toxicity. The incidence and severity of late toxicity was acceptable, with 32% Grade 3 and no Grade 4 toxicity. The protocol of concomitant chemoradiotherapy using tegafur-uracil, leucovorin, and carboplatin for locally advanced unresectable head-and-neck squamous cell carcinoma is feasible. The compliance was correct. The incidence and severity of the acute and late toxicities were acceptable, but not improved. The efficacy of this regimen seems equivalent to the main protocols of concurrent chemoradiotherapy. It represents a possible alternative for patients without an intravenous catheter.

Exclusive radiotherapy for primary squamous cell carcinoma of the vagina

Purpose To retrospectively analyze results of external beam therapy (EBT) with brachytherapy (BT) for primary vaginal squamous cell carcinoma (PVSCC). Materials and methods From 1970 to 2001, 91 patients were included. FIGO stages were: I (29%), II (38%), III (29%) and IVa (4%). EBT delivered a median total dose of 50 Gy to the pelvis. BT was performed with a customized intra-vaginal applicator and in 36% of applications combined endocavitary and interstitial BT. ICRU Report 38 parameters were reported. Results The 5-year cause specific survival (CSS) rates were: 83% for stage I, 76% for stage II, 52% for stage III, and 2 of the 4 stage IVa patients died 9 and 36 months after treatment. The 5-year pelvis control rates were: 79% for stage I and II and 62% for stage III. Recurrences as a first event were local only in 68% of cases, nodal only in 10%, metastatic only in 13% and combined in 9%. In multivariate analysis: stage (I and II versus II and IV), response to EBT (evaluated at BT), and the number of BT applications were statistically significant for CSS. Grade 2–3 toxicities were as follows (Franco-Italian Glossary): rectum ( n = 3), sigmoid colon and small bowel ( n = 8), bladder ( n = 5), ureter ( n = 4) and vagina ( n = 13). Anterior location of the tumor increased bladder toxicity ( p = 0.01) and total reference air kerma was higher in patients who experienced grade 2–3 urinary or digestive toxicity ( p = 0.03). Conclusion EBT with BT is an effective treatment for patients with stage I–II PVSCC. The incidence and severity of late toxicity were relatively low. Recent advances in the treatment of cervix carcinoma emphasize the need for concomitant radio-chemotherapy in stages III–IV and the use of MRI for treatment planning.