Duration of acute esophageal toxicity in concomitant radio-chemotherapy for non-small cell lung cancer with different fractionation schedules.

OBJECTIVES: In our previous prospective trial on accelerated hypofractionated concomitant radiochemotherapy (AHRT-CHT) for non-small-cell lung cancer (NSCLC), the incidence of grade ≥3 acute esophageal toxicity (AET) was similar to that reported for conventionally fractionated concomitant radiochemotherapy (CFRT-CHT), but its duration was prolonged. Thus, we aimed to compare the duration of grade ≥3 AET between AHRT-CHT and CFRT-CHT. METHODS: Clinical data of 76 NSCLC patients treated with CFRT-CHT (60-66 Gy/2 Gy) during 2015-2020 were retrospectively compared with the data of 92 patients treated with AHRT-CHT (58.8 Gy/2.8 Gy) in the prospective trial. The maximum grade of AET, incidence, and duration of grade ≥3 AET were the end points. Univariate and multivariate analyses were applied to correlate clinical and treatment variables with these end points. RESULTS: Neither the maximum grade of AET (p = 0.71), nor the incidence of grade ≥3 AET (p = 0.87) differed between the two groups. The number of CHT cycles delivered (2 vs 1, p = 0.005) and higher esophagus mean BED (p = 0.009) were significant predictors for a higher maximum grade of AET; older age was a significant predictor for higher incidence of grade ≥3 AET (p = 0.03). The median duration of grade ≥3 AET in AHRT-CHT and CFRT-CHT group was 30 days (range 5-150) vs 7 days (range 3-20), respectively, p = 0.0005. In multivariate analysis, only the AHRT-CHT schedule (p=0.003) was a significant predictor for a longer duration of grade ≥3 AET. CONCLUSION: Despite similar incidence of grade ≥3 AET, its duration is significantly prolonged in NSCLC patients treated with AHRT-CHT compared to CFRT-CHT. ADVANCES IN KNOWLEDGE: Reporting only the rate of grade ≥3 AET in clinical trials may underestimate the real extent of the esophageal toxicity; its duration should also be routinely reported.

Postoperative radio-chemotherapy for rectal cancer: A retrospective analysis from a tertiary referral hospital.

AIM: To report results of postoperative radio-chemotherapy (RT-CHT) for rectal cancer (RC). BACKGROUND: Total mesorectal excision (TME) is an essential treatment method in rectal cancer (RC). Perioperative radiotherapy in locally advanced RC improves loco-regional free survival (LRFS). Preoperative radiotherapy is a preferred option; however, some patients are not referred for it. In case of the risk of loco-regional failure postoperative radio-chemotherapy (RT-CHT) is indicated. MATERIAL AND METHODS: Between 2004 and 2010, 182 patients with pathological stage II-III RC (TME performed - 41%, resection R0 - 88%, circumferential resection margin evaluated - 55.5% and was above 2 mm in 66% of them) received postoperative RT-CHT in our institution. Overall survival (OS) and LRFS were estimated with the Kaplan-Meier method. Univariate and multivariate analysis were performed to compare the impact of prognostic factors on survival. RESULTS: Five-year OS and LRFS rates were 63% and 85%, respectively. Loco-regional recurrence and isolated distant metastases rates were 11.5% and 19%, respectively. Multivariate analysis showed stage (III vs. II), HR: 2.3 (95% confidence interval [CI]: 1.4-3.8), p = 0.0001; extent of resection (R1-2 vs. R0), HR: 2.14 (95%CI: 1.14-3.99), p = 0.017, and age (>65 vs. ≤65 years), HR: 1.66 (95%CI: 1.06-2.61), p = 0.027 as prognostic factors for OS. Extent of resection (R1-2 vs. R0), HR: 3.65 (95%CI: 1.41-9.43), p = 0.008 had significant impact on LRFS. CONCLUSION: Despite a suboptimal quality of surgery and pathological reports, the outcome in our series is close to that reported in the literature. We confirm a strong impact of the extent of resection on patient's outcome, which confirms the pivotal role of surgery in the management of RC.

Accelerated hypofractionated radiotherapy with concurrent full dose chemotherapy for locally advanced non-small cell lung cancer: A phase I/II study.

INTRODUCTION: We report the results of toxicity and survival in stage III NSCLC patients treated with concurrent accelerated hypofractionated AHRT-CHT within a prospective study. METHODS: 92 patients received 3D-CRT or IMRT-planned RT: 58.8 Gy /21 fractions (2.8 Gy/fraction, 4 weeks) with 2 cycles of CHT (Cisplatin 80 mg/m2 D1 and D22; and Vinorelbine 25 mg/m2, D1, D8, D22, and D29) started with D1 of RT. Non-hematological toxicity was evaluated using RTOG-EORTC criteria, every week during treatment, one month after treatment completion, and every three months thereafter. RESULTS: Two patients did not receive the prescribed RT dose; 22 (24%) received only one CHT cycle. Median follow-up was 21.5 months (range: 1-65) for all patients and 32 months (range: 8-65) for living patients. There were: 13 (14%) cases of grade ≥III acute esophageal toxicity; 3 grade III acute pneumonitis, and 2 grade III late pulmonary toxicities. Two toxic deaths occurred within 3 months after treatment: fatal hemoptysis (1) and complications of esophageal toxicity (1). Five other deaths that occurred within one year after treatment were probably treatment-related: lung abscess (1), fatal hemoptysis (2), death from undetermined cause (2). Median overall survival was 38 months (95%CI:27-49), median progression free survival was 25 months (95%CI:14-36). CONCLUSIONS: Survival rates are encouraging, but the observed rate of toxic and probably toxic deaths is of potential concern. We proceed with the use of AHRT with concomitant full dose CHT, but patients with large PTV and major vascular abutment are excluded due to potentially increased risk of toxic death.

Stereotactic radiotherapy of the tumor bed compared to whole brain radiotherapy after surgery of single brain metastasis: Results from a randomized trial.

PURPOSE: To evaluate if neurological/cognitive function outcomes in patients with resected single brain metastasis (BM) after stereotactic radiotherapy of the tumor bed (SRT-TB) are not inferior compared to those achieved with whole-brain radiotherapy (WBRT). METHODS: Patients with total/subtotal resection of single BM were randomly assigned either to SRT-TB (n=29) or WBRT (n=30). SRT-TB arm consisted of 15Gy/1 fraction, or 5×5Gy. WBRT consisted of 30Gy/10 fractions. Neurological/cognitive failure was defined as a decrease of neurological score by one point or more, or a worsening of the MiniMental test by at least 3 points, or neurological death. Cumulative incidence of neurological/cognitive failure (CINCF), neurological death (CIND), and overall survival (OS) were compared. RESULTS: Median follow-up was 29months (range: 8-45) for 15 patients still alive. The difference in the probability of CINCF at 6months (primary endpoint) was -8% in favor of WBRT (95% confidence interval: +17% -35%; non-inferiority margin: -20%). In the intention-to-treat analysis, two-year CIND rates were 66% vs. 31%, for SRT-TB and WBRT arm, respectively, p=.015. The corresponding figures for OS were 10% vs. 37%, p=.046. CONCLUSIONS: Non-inferiority of SRT-TB was not demonstrated in our underpowered study. More data from randomized studies are needed for confirmation of the value of this method.

Sequencing postoperative radiotherapy and adjuvant chemotherapy in non-small cell lung cancer: unanswered questions on the not evidence-based approach.

This editorial comments on the study by Lee et al. which reported on the use of postoperative radiotherapy (PORT) as first strategy after resection of stage IIIA-pN2 non-small cell lung cancer (NSCLC). After completion of PORT, 41% of patients received postoperative chemotherapy (POCT). The five-year overall survival (OS) was significantly higher in patients treated with PORT and POCT than in patients treated with PORT alone. Authors concluded that PORT used as first postoperative strategy does not compromise a benefit of POCT and its implementation should be further studied. We discuss the pros and cons of using PORT before POCT for stage IIIA-pN2 NSCLC. Some radiobiological data support earlier use of PORT, however, caution should be paid to not to unnecessarily delay or omit POCT because of its demonstrated survival benefit. Concurrent postoperative radio-chemotherapy could be an attractive approach, but we still have very limited clinical data on its use in this indication.

The outcomes of Polish patients with advanced BRAF-positive melanoma treated with vemurafenib in a safety clinical trial.

AIM OF THE STUDY: The BRAF inhibitor vemurafenib has improved progression-free survival and overall survival in patients with BRAFV600-mutation-positive metastatic melanoma. Here we present the results of an open-label safety study with vemurafenib in patients with metastatic melanoma enrolled in Polish oncological centres. MATERIAL AND METHODS: Patients with untreated or previously treated Stage IIIC/IV BRAFV600 mutation-positive melanoma were treated with oral vemurafenib in an initial dose of 960 mg twice daily. Assessments for safety and efficacy were made every 28 days. For the survival analysis the Kaplan-Meier estimator was used with the log-rank tests for bivariate comparisons. RESULTS: In total, 75 Polish patients were enrolled in the safety study across four centres. At data cut-off, 28 patients died (37%), mainly (26) due to disease progression; 33 (44%) patients continued vemurafenib after disease progression. The objective response rate was 46%, including two patients with a complete response and 29 with a partial response. Median progression-free survival was 7.4 months. The one-year overall survival rate was 61.9% (median overall survival was not reached). Seventy-three (97.3%) patients reported adverse events (AEs), and grade 3-5 toxicity was reported in 49.4% (37) patients. The most common AEs were: skin lesions (including rash and photosensitivity), arthralgia, and fatigue. CONCLUSIONS: The overall safety profile and response rate of vemurafenib were comparable to those reported in previous studies of this drug. Our study confirmed the value of well-established prognostic features for overall survival, such as initial LDH (lactate dehydrogenase) level and AJCC staging.

Smoking during radiotherapy for head and neck cancer and acute mucosal reaction.

AIM: We compared the incidence of RTOG/EORTC grade III and higher acute mucositis in patients with head and neck cancer who continued to smoke during radiotherapy with those who quit smoking. BACKGROUND: There are conflicting data on the relationship between smoking during radiotherapy and the severity of acute mucosal reaction. More studies dealing with this issue are needed. MATERIALS AND METHODS: Among 136 patients receiving curative radio(chemo)therapy, 37 (27%) declared that they had not quit smoking during radiotherapy. The intensity of mucositis was scored daily by a nurse and weekly by a physician using the RTOG/EORTC scale. The main end-point of the study was the highest observed RTOG/EORTC grade of mucositis. RESULTS: Patients who smoked during radiotherapy (smokers) were younger than their counterparts who quit smoking (non-smokers), p = 0.06. There were no other differences in the baseline characteristics between smokers and non-smokers. Grade III/IV acute mucositis was observed in 43.5% of all patients. The percentage of patients with grade III/IV acute mucositis was similar in smokers and non-smokers (46% vs. 42%, p = 0.71). Nine patients (smokers [13.5%]; non-smokers [4%], p = 0.05) required prolonged hospitalization to heal mucositis. CONCLUSIONS: In the whole group, smoking during radiotherapy was not related to acute mucosal toxicity evaluated as the rate of the highest observed grade of mucositis.

Clinical outcome and toxicity of 3D-conformal radiotherapy combined with chemotherapy based on the Intergroup SWOG 9008/INT0116 study protocol for gastric cancer.

PURPOSE: To retrospectively evaluate the efficacy and toxicity of adjuvant radio-chemotherapy in patients with gastric cancer and to relate them to the outcome of the landmark INT0116 study that is criticized because of the high toxicity and poor treatment compliance. METHODS: A total of 102 patients who underwent postoperative fluorouracil (5-FU)-based radio-chemotherapy in our institution between 2004 and 2010 for stage IB-IV (AJCC 6th Edn.) gastric cancer were selected. Radiotherapy to 45 Gy was defined individually and delivered with 3D conformal technique. Chemotherapy was carried out during the first 4 and the last 3 days of radiotherapy with continuous infusion of 5-FU (400mg/m²/day) and leucovorin. Patients received an additional 3 cycles of chemotherapy of 5-FU (425mg/m²/day), mostly 1 before and 2 after radio-chemotherapy. Acute hematological and gastrointestinal toxicities were evaluated according to the CTC v3.0 scale. RESULTS: Stage distribution was as follows: IB-5 (5%), II-32 (31%), III-49 (48%), and IV-14 (14%). There were 96% R0 resections; 15% of the patients had a D2 resection. Seventy-four patients (72.5%) received all 5 planned cycles and 98 (96%) completed radiotherapy. The 3- and 5-year overall survival (OS) rates were 57% and 48%, respectively. Multivariate analysis showed that variables significantly affecting OS were pT3-T4, pN2-3, R1 resection and female gender. Only 2% of the patients experienced grade 3 gastrointestinal toxicity; 7% had grade 3 or higher hematological toxicity. CONCLUSIONS: We demonstrated better treatment tolerance, compliance, OS of adjuvant radio-chemotherapy for gastric cancer in comparison with INT0116 study. Conformal radiation techniques might have contributed to this improvement.

Concurrent chemotherapy and short course radiotherapy in patients with stage IIIA to IIIB non-small cell lung cancer not eligible for radical treatment: results of a randomized phase II study.

INTRODUCTION: The optimal treatment for patients with stage IIIA to IIIB non-small cell lung cancer (NSCLC) not eligible for surgery and definitive chemoradiotherapy is unknown. The aim of this study was to evaluate concurrent chemotherapy and palliative radiotherapy. METHODS: Patients with stage IIIA to IIIB NSCLC with tumor >8 cm and/or forced expiratory volume < or =40%, performance status 0 to 2, and tumor-related chest symptoms were randomly assigned to arm A: radiotherapy alone (30 Gy/10 fractions) or arm B: chemoradiotherapy (two cycles of cisplatin and vinorelbine followed by radiotherapy together with third cycle). Primary end point was response rate, the power of the study was 90%, and the significance level was p = 0.1. RESULTS: A total of 99 patients were eligible for response, overall survival, and progression-free survival evaluation. Median age was 66 years (45-78 years). Response rate was 27% versus 53%, p = 0.08; median overall survival was 9.0 versus 12.9 months, p = 0.0342; and median progression-free survival was 4.7 versus 7.3 months, p = 0.046, in arm A versus arm B, respectively. There were no deaths during treatment in arm A and six deaths in arm B; no hematological G3 to G4 toxicities in arm A and 14 toxicities in arm B. Symptom control was high and similar in both arms. CONCLUSIONS: Upfront chemotherapy combined with palliative radiotherapy (30 Gy) is a promising treatment option in the subpopulation of patients with stage IIIA to IIIB NSCLC not amenable for definitive chemoradiotherapy and deserves further investigation.

[Results of treatment in patients with paranasal sinus carcinoma. Analysis of prognostic factors]. / Wyniki leczenia chorych na raka zatok obocznych nosa. Analiza czynników prognostycznych.

Analysis was based on the results of successful and unsuccessful treatment of 137 patients with paranasal sinus cancer at the Oncology Centre in Warsaw between 1987-2002. Patients with clinical stages T3 and T4 constituted 87% of cases (110 patients). Radical treatment was performed on 84 patients. Five-year overall survival in 137 cases amounted to 27%; and survival without recurrence was 24%. Five-year overall and recurrence-free survial among patients treated with surgery and radiotherapy were 36% and 32% retrospectively. Multivariate analysis of 61 patients with complete data, who were treated with radical surgery and radiotherapy, emphasized the influence of prognostic factors on survival. A worse prognosis correlated with advanced locoregional T and N stage. It is evident that total dose greater than 6000 cGy had a clear impact on the results of treatment. It was also shown that planning with the manually and hand-measured isodoses impacted negatively on the survival in comparison with 2D and 3D planning. Analysis of recurrence-free survival showed that metastatis to the lymph nodes, and a manually-planned treatment method, had a negative impact on the results of treatment. It is asserted that local recurrences are the main cause of failure in cases treated with surgery and radiotherapy.

[The role of hemoglobin concentration in the outcome of definitive radiotherapy of the oropharyngeal cancer]. / Ocena wplywu steqenia hemoglobiny na wyniki radykalnego leczenia napromienianiem chorych na raka ustnej czesci gardla.

INTRODUCTION: Squamous cell carcinoma of the oropharynx is potentially curative by radiotherapy. The impact on the treatment results have factors related to neoplasm, to the patient and factors related to the method of radiotherapy. The aim of this paper is evaluation of the impact of hemoglobin concentration (Hb) on treatment results in these patients. METHODS: 241 patients with squamous cell carcinoma of the oropharynx were treated between 1984-1995 in Radiotherapy Department II of Centre of Oncology in Warsaw. Most of them had locally and regionally advanced disease (T3-T4 in 63% and N2-3 in 41% of the patients). The pretreatment level of Hg was determined. All patients underwent definitive radiotherapy with the mean total dose 66-70 Gy. RESULTS: The estimated 5-year overall survival in this group was 23%. Analysis of clinical factors and factors related to the treatment has shown independent impact of the Hb concentration on radiotherapy results. In the group of patients with Hb level above 13 g/dL the risk of death and risk of locoregional recurrance were two times lower in comparison with group where Hb level was equal to or below 13 g/dL (p = 0.0002 and p = 0.013 respectively). CONCLUSION: In the group of the patients with squamous cell carcinoma of the oropharynx, Hb concentration is important prognostic factor of the local control probablility and overall survival.

[Lymphatic metastasis in the neck from unknown primary. Analysis of treatment results and prognostic factors]. / Przerzuty do wezlów chlonnych szyi z nieznanego ogniska pierwotnego. Analiza wyników leczenia i czynników rokowniczych.

The aim of this study is to analyze the results of treatment results and prognostic factors related to clinical and treatment characteristics in patients with neck lymph nodes metastases from the unknown primary site. 90 patients with pathology proven cancer metastases in the neck lymph nodes from the unknown primary site were treated between 1984-1998. Most of them (58 patients--63%) had advanced disease in lymph nodes N3. The rest had stage N2abc before initial treatment. 40 patients underwent combined treatment--surgery and definitive radiotherapy. 3 patients had induction chemotherapy followed by resection and radiotherapy. 30 patients received radiotherapy alone or radiotherapy and chemotherapy. In 7 cases chemotherapy after surgical resection were used. Curves of overall survival were estimated using Kaplan-Meier method. Analysis of the prognostic factors was performed using Cox's multivariate proportional risk model. 5 years overall survival probability was 24%. In the group of patients who underwent surgery and radiotherapy probability of 5 years overall survival was 43%. In patients who received radiotherapy alone or radiotherapy and chemotherapy probability of 5 year overall survival was 2%. Multivariate analysis showed significant influence of the performance status (PS--WHO scale), sex and stage N3 on overall survival. The patients with PS 0-1 had better prognosis comparing with PS 2-3 (p < 0.001). Male had worse prognosis then female (p = 0.05). N3 stage reduced overall survival in comparison to N2abc (p = 0.06). In the analysis of disease free survival N3-stage was the only independent factor concerning with poor outcome (p = 0.03). Patients who had surgery followed by radiotherapy had better prognosis. Poor performance status, sex-male and N3 stage were identified as the important factors influencing overall survival. N3-stage was an independent factor influencing disease free survival.