Toxicity Of Concurrent Chemoradiation Research Articles

Dosimetric correlation of bone marrow irradiation with acute hematological toxicity in concurrent chemoradiation of cervical carcinoma patients.

Many acute toxicities are associated with concurrent chemoradiation in cervical carcinoma, which includes burning micturition, burning defecation, pain lower abdomen, increased frequency of stools along with Acute Hematological Toxicity (AHT). AHT is often an expected adverse effect, which can lead to treatment interruptions and decreased response rates. The purpose of this study is to analyze if there are any dosimetric constraints on the volume of bone marrow irradiated with AHT in cervical carcinoma patients treated with concurrent chemoradiation. In this retrospective study of 215 patients, a total of 180 patients were eligible for analysis. Multiple parameters of bone marrow volumes (whole pelvis bone marrow and its sub-volumes--ilium, lower pelvis, and lumbosacral spine) which were contoured individually for all patients were assessed to have any statistically significant association with AHT. The median age of the cohort was 57 years and majority of cases were locally advanced (stage IIB-IVA: 88.3%). Grade I, II, III leukopenia was seen in 44, 25, and 6 patients, respectively. A statistically significant correlation between grade 2+ and 3+ leukopenia was seen if bone marrow V10, V20, V30, and V40 were more than 95%, 82%, 62%, and 38%, respectively. In subvolume analysis, volumes of lumbosacral spine V20, V30, and V40 more than 95%, 90%, and 65%, respectively, were statistically significant for AHT. Bone marrow volumes should also be given a constraint and should be tried to be achieved so that it leads to minimal treatment breaks due to AHT.

Unhealthy alcohol use and toxicity of concurrent chemoradiation for head and neck cancer.

e17559 Background: Unhealthy alcohol use (UAU) is an important risk factor for development head and neck squamous cell carcinoma (HNSCC), but any effect on treatment outcomes is not well understood. The Veterans Health Administration (VHA) annually screens outpatients for UAU with the validated Alcohol Use Disorders Identification Test Consumption (AUDIT-C). Methods: Using national VHA data we retrospectively identified patients administered upfront radiation with concurrent systemic therapy (chemo- and/or immuno- therapy) for stage III-IVb HNSCC diagnosed 2008 –2017 and included males with a prior-year AUDIT-C. Regression models were fit to assess associations between AUDIT-C risk groups [low-level use (score 1-3), moderate UAU (4-7), severe UAU (≥ 8)] and treatment toxicity. Models were adjusted for a priori defined covariates including smoking and variables related to demographics, comorbidities, and cancer diagnosis and treatment. Results: Among 3,094 patients, 46.7% screened positive for UAU: 23.9% with moderate UAU and 22.9% with severe UAU. Compared to patients with low-level alcohol use, those with severe UAU were younger (mean age 65 vs 67 years) and more frequently active smokers (63.4% vs 36.2%) and underweight (11.2% vs 3.5%) ( p for all comparisons < 0.05). There was no significant difference between alcohol use groups in race/ethnicity, cancer stage, or systemic treatment agent used. In adjusted models, severe UAU was associated with lower risk of nausea [adjusted odds ratio (AOR) 0.63, 95% CI 0.47 – 0.84], ED visits (AOR 0.79, CI 0.63 – 0.99), and hospitalizations during treatment (AOR 0.78, CI 0.62 – 0.98). UAU was not associated with a composite measure of complications of infection or organ damage (AOR 0.94, CI 0.74 – 1.20), severe weight loss (AOR 0.83, CI 0.66 – 1.05), or mortality within 100 days of completing treatment (AOR 1.01, CI 0.62 – 1.66). Conclusions: In this large cohort of male patients in the VHA treated for locoregionally advanced HNSCC with concurrent chemoradiation, moderate and severe UAU is common. UAU is not associated with increased toxicity of treatment, and future research is required to define its place in treatment selection, supportive care, and counseling.

Chemoradiation in elderly patients with head and neck cancers: a single institution experience

AimsTo evaluate the efficacy and toxicity of concurrent chemoradiation in patients with head and neck cancers aged 65 and older. Materials and methodsThirty-two elderly patients were treated with radical chemoradiation. Twenty-six (81.3%) out of thirty-two patients had stage III–IV disease. Twenty-nine (90.6%) patients received concurrent weekly cisplatin or carboplatin, 3 (9.4%) patients received concurrent cetuximab or nimotuzumab. Total dose of radiotherapy ranged from 66Gy to 70Gy. ResultsTwenty-nine patients (90.6%) completed at least 5cycles of concurrent chemotherapy. Twenty-four (77.6%) patients achieved complete response. Fourteen (45.2%) patients experienced grade 3 mucositis. None of our patients developed grade 3 or above hematological toxicity. Loco-regional control and overall survival at 2year were 71.6% and 88.9%, respectively. ConclusionsChemoradiation in elderly patients with high precision radiotherapy is a feasible option.

A Phase 2 Trial of Radiation Therapy With Concurrent Paclitaxel Chemotherapy After Surgery in Patients With High-Risk Endometrial Cancer: A Korean Gynecologic Oncologic Group Study

A phase 2 study was completed by the Korean Gynecologic Oncologic Group to evaluate the efficacy and toxicity of concurrent chemoradiation with weekly paclitaxel in patients with high-risk endometrial cancer. Pathologic requirements included endometrial endometrioid adenocarcinoma stages III and IV. Radiation therapy consisted of a total dose of 4500 to 5040 cGy in 5 fractions per week for 6 weeks. Paclitaxel 60 mg/m(2) was administered once weekly for 5 weeks during radiation therapy. Fifty-seven patients were enrolled between January 2006 and March 2008. The median follow-up time was 60.0 months (95% confidence interval [CI], 51.0-58.2). All grade 3/4 toxicities were hematologic and usually self-limited. There was no life-threatening toxicity. The cumulative incidence of intrapelvic recurrence sites was 1.9% (1/52), and the cumulative incidence of extrapelvic recurrence sites was 34.6% (18/52). The estimated 5-year disease-free and overall survival rates were 63.5% (95% CI, 50.4-76.5) and 82.7% (95% CI, 72.4-92.9), respectively. Concurrent chemoradiation with weekly paclitaxel is well tolerated and seems to be effective for high-risk endometrioid endometrial cancers. This approach appears reasonable to be tested for efficacy in a prospective, randomized controlled study.

Concurrent chemoradiation with paclitaxel in high-risk endometrial cancer patients after surgery: A Korean Gynecologic Oncology Group study

Objectives: To evaluate the efficacy and toxicity of concurrent chemoradiation with weekly paclitaxel in patients with high-risk endometrial cancer.

Chemoradiation With Paclitaxel and Carboplatin in High-Risk Cervical Cancer Patients After Radical Hysterectomy: A Korean Gynecologic Oncology Group Study

To evaluate the efficacy and toxicity of concurrent chemoradiation with paclitaxel and carboplatin in patients with high-risk cervical cancer. Patients after radical hysterectomy for cervical cancer, with at least 1 high-risk characteristic, were administered paclitaxel 135 mg/m(2), carboplatin area under the curve = 5 every 3 weeks for 3 cycles concomitant with radiation therapy as adjuvant treatment. This prospective study enrolled 71 consecutive patients. Sixty-six patients (93%) completed the planned treatment. The majority of grade 3/4 neutropenia or nonhematologic toxicities were usually self-limited. Diarrhea grades 3/4 were observed in 4 patients (5.6%). One patient developed anaphylactic shock after infusion of paclitaxel. With a median follow-up of 57 months, recurrences occurred in 16 patients. Multivariable analysis indicated that common iliac lymph node involvement is an independent risk factor for disease recurrence (odds ratio 13.48; 95% confidence interval 2.93-62.03). In the intent-to-treat population (n=71), the estimated 5-year disease-free survival and overall survival rates were 77.3% and 80.3% respectively. In the per-protocol population (n=62), disease-free survival was 78.9% and overall survival was 83.9%. Concurrent chemoradiation with paclitaxel/carboplatin is well tolerated and seems to be effective for patients who undergo radical hysterectomy. Therefore, a prospective, randomized controlled study should be designed to evaluate efficacy of this approach for patients with high-risk cervical cancer.

Concurrent Chemoradiation in Inoperable, Locally Advanced Non-small Cell Lung Cancer—Comparison of Efficacy and Toxicity in the Elderly

Clinicians are faced with the challenge of treating increasing numbers of elderly patients with locally advanced non-small cell lung cancer (LA-NSCLC) and comorbid conditions. In the younger patient, the benefit of combined chemoradiation using the concurrent modality compared with the sequential administration of both modalities has been established in several randomised trials and recent meta-analyses. Because of the underrepresentation of elderly patients in clinical trials on concurrent chemoradiation (CCRT) in LA-NSCLC, treatment guidelines for this age group are not well established. The objective of this article is to summarise the data on efficacy and toxicity of CCRT in the elderly.

Concurrent Chemoradiation in Inoperable, Locally Advanced Non-small Cell Lung Cancer — Comparison of Efficacy and Toxicity in the Elderly

Clinicians are faced with the challenge of treating increasing numbers of elderly patients with locally advanced non-small cell lung cancer (LA-NSCLC) and co-morbid conditions. The benefit of combined chemoradiation in the younger patient using the concurrent modality compared with the sequential administration of both modalities has been established in several randomised trials and recent meta-analyses. Because of the underrepresentation of elderly patients in clinical trials on concurrent chemoradiation (CCRT) in LA-NSCLC, treatment guidelines for this age group are not well established. The objective of this report is to summarise the data on efficacy and toxicity of CCRT in the elderly.

The effect of treatment position, prone or supine, on dose–volume histograms for pelvic radiotherapy in patients with rectal cancer

Patients undergoing radiotherapy for rectal cancer are generally treated in a prone position, with a full bladder, to reduce the volume of normal bowel in the high-dose volume. This position is difficult to maintain, and is not consistently reproducible. This study evaluates the volume of bowel and dose received in the prone and supine positions in patients undergoing pre-operative rectal cancer chemoradiation. Using CT planning, 19 consecutive patients with rectal cancer with a full bladder underwent CT scanning first in the prone position and then immediately afterwards in the supine position. The planning target volume was outlined for the prone position and transcribed to the supine scan using pre-set criteria. The bladder and small bowel were outlined in both positions. Radiotherapy was planned using three-dimensional conformal planning, and treatment was delivered using three fields with multileaf collimators in two phases: phase I, pelvis 45 Gy/25 fractions; and phase II, tumour 9 Gy/five fractions. For both positions, the volume of bowel receiving doses in 5 Gy increments from 5-45 Gy was calculated using dose-volume histograms. At 5 Gy and 10 Gy dose levels, a significantly higher volume of bowel was irradiated in the supine position (p<0.001). At 15 Gy, it was marginally significant (p = 0.018). From 20-45 Gy, there was no significant difference in the volume of bowel irradiated with each 5 Gy increment. This study demonstrates that the volume of bowel irradiated at doses associated with bowel toxicity in concurrent chemoradiation is not significantly higher in the supine position. This position could be adopted for patients undergoing pre-operative rectal cancer chemoradiation.

Tolerability assessment of urasil-tegafur (UFT)/folinic acid (FA) as concurrent chemoradiation (CRT) in adjuvant rectal cancer treatment

13559 Background: The objective of the present phase II study was to evaluate the feasibility of UFT and FA as a concomittant CRT administration for rectal cancer in the adjuvant setting. Methods: Between October 2003 and December 2005 thirty-one (10 female; 21 male) patients were treated. All the patients were locally advanced (T2N1–2M0 (2), T3N0M0 (12), T3–4N1M0 (9), T3–4N2M0 (7)) and median age was 62 (range, 21–85). Inclusion criteria were WHO 0–1, age ≥ 18, complete tumor resection, stage T3/4 or N+, adequate CBC, liver function tests and signed informed consent form. RT was performed in 8 weeks following the surgery and the dose was 50.4 Gy given at 1.8 Gy daily. Chemotherapy consisted of UFT (300 mg/m2/day) and FA (30 mg/day) during week-days of radiotherapy and continued 4 cycles with same dose (D1–28/35days) after CRT. Acute toxicity was assessed according to CTC 2.0 criteria. Results: Median follow-up for all patients was 12 months (between 3–27 months). No toxic death occurred. CRT related side effects were diarrhea Gr 2 (25%) and Gr 3 (25%); emesis Gr 2 (29%) and Gr 3 (10%); dysuria Gr 2 (10%) and Gr 3 (10%). All patients completed radiotherapy but 21 out of 31 (67%) continued with UFT/LV until the end of concurrent treatment. The full compliance to the adjuvant CT part was 63%. During the adjuvant CT period there were diarrhea Gr 3–4 (10%), emesis Gr 3 (10%) and no Gr 3–4 hematological toxicity observed during the whole treatment. During the study period none of the patients failed locally, 3 patients developed distant metastases (2 liver, 1 bone), and 3 patients died (1 with disease, 2 without). Two-year disease-free and overall survival rates were 84% and 71%, respectively. Conclusion: The acute and subacute toxicity of CRT with UFT/LV is acceptable and seems comparable to infusional 5-FU based combined modality treatments. No significant financial relationships to disclose.

Effect of Chemoradiotherapy with Gemcitabine and Cisplatin on Locoregional Control in Patients with Primary Inoperable Pancreatic Cancer

Gemcitabine sensitizes tumor cells to radiation and cisplatin and thereby enhances the cytotoxic effect of gemcitabine. Here we report the efficacy and toxicity of concurrent chemoradiation with gemcitabine and cisplatin in the treatment of patients with locally advanced, unresectable pancreatic cancer. A total of 47 patients (29 men, 18 women; median age 61 years) with histologically proven advanced pancreatic carcinoma were included in the study. They underwent chemotherapy with gemcitabine 300 mg/m2 and cisplatin 30 mg/m2 on days 1, 8, 22, and 29; concurrent radiation (45-50 Gy) was applied to the tumor and regional lymph nodes (1.8-2.0 Gy/fraction 5 days per week). Subsequent to chemoradiotherapy, treatment was continued with more two cycles of gemcitabine (1000 mg/m2) and cisplatin (50 mg/m2) applied on days 1 and 15 of a 4-week cycle. After completion of chemoradiotherapy, 9 patients (19.1%) achieved a complete response and 23 patients (48.9%) a partial response, for an overall response rate of 68%. The lesions were considered resectable in 27 patients, and 25 of the 27 patients underwent laparotomy. The other 20 patients underwent a definitive pancreatic resection. Altogether, 13 patients had negative surgical margins. With a median follow-up of 25.7 months (range 12.7-38.7 months) after completion of chemoradiation, distant metastasis had occurred in 23 patients and local recurrence in only 4 of 44 patients (8.5%). the median progression-free survival was 7.8 months (range 6.2-9.4 months). The median survival amounted to 10.7 months (range 8.4-13.0 months) for all patients, whereas it was prolonged to 24.2 months (range 6.8-41.7 months) for those undergoing R0 resection. The main toxicities associated with chemoradiation included grade 3/4 leukopenia (68% of patients) and thrombocytopenia (61%). Episodes of cholangitis were observed in 11 patients. We concluded that gemcitabine and cisplatin can safely be combined with external beam radiation. This preoperative treatment approach is highly effective and appears to improve survival in patients whose tumors are rendered completely resectable.