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.

Neoadjuvant chemotherapy with or without oxaliplatin after short-course radiotherapy in high-risk rectal cancer: A subgroup analysis from a prospective study.

AIM: To evaluate the role of oxaliplatin in neoadjuvant chemotherapy delivered after short-course irradiation. BACKGROUND: Using oxaliplatin in the above setting is uncertain. PATIENTS AND METHODS: A subgroup of 136 patients managed by short-course radiotherapy and 3 cycles of consolidation chemotherapy within the framework of a randomised study was included in this post-hoc analysis. Sixty-seven patients received FOLFOX4 (oxaliplatin group) while oxaliplatin was omitted in the second period of accrual in 69 patients because of protocol amendment (fluorouracil-only group). RESULTS: Grade 3+ acute toxicity from neoadjuvant treatment was observed in 30% of patients in the oxaliplatin group vs. 16% in the fluorouracil-only group (p = 0.053). The corresponding proportions of patients having radical surgery or achieving complete pathological response were 72% vs. 77% (odds ratio [OR] = 0.88; 95% confidence interval [CI]: 0.39-1.98; p = 0.75) and 15% vs. 7% (OR = 2.25; 95% CI: 0.83-6.94; p = 0.16), respectively. The long-term outcomes were similar in the two groups. Overall and disease-free survival rates at 5 years were 63% vs. 56% (p = 0.78) and 49% vs. 44% (p = 0.59), respectively. The corresponding numbers for cumulative incidence of local failure or distant metastases were 33% vs. 38% (hazard ratio [HR] = 0.89; 95% CI: 0.52-1.52; p = 0.68) and 33% vs. 33% (HR = 0.78; 95% CI: 0.43-1.40; p = 0.41), respectively. CONCLUSION: Our findings do not support adding oxaliplatin to three cycles of chemotherapy delivered after short-course irradiation.

Selection of patients with left breast cancer for deep-inspiration breath-hold radiotherapy technique: Results of a prospective study.

AIM: To assess prospectively which patients with left breast cancer have the dosimetric benefit from the use of deep-inspiration breath-hold radiotherapy (DIBH-RT). BACKGROUND: Improvement in selection of patients for DIBH-RT would spare time of radiotherapy staff by removing the need for preparation of two comparative treatment plans. MATERIALS AND METHODS: Thirty-one patients qualified for whole left breast irradiation underwent breath-hold training and their free-breathing (FB) and DIBH planning-CT were included in the analysis of dosimetric outcome. Mean heart dose (MHD), heart V20 Gy (V20Heart), maximum dose to LAD (LADmax), V20 for left lung (V20L.lung) were recorded from FB and DIBH plans and the differences (Δ) of these values were calculated. If relative improvement of at least 20% for any evaluated dosimetric parameter was found for the DIBH-RT, this plan was selected for treatment. Correlations of Δ of dosimetric parameters with patient-related parameters (BMI, age, PTV, cardiac contact distance [CCD], lung volume at FB) were sought. RESULTS: In 30 of 31 patients, a predefined reduction in evaluated parameters was achieved. CCD, BMI correlated positively with ΔMHD, ΔV20Heart, ΔLADmax; PTV with ΔMHD and ΔV20Heart (p < 0.05; AUC > 0.6); Lung volume correlated negatively with ΔLADmax, ΔMHD and ΔV20Heart. No specific thresholds for the lack of predefined improvement of any dosimetric parameters was identified in ROC analysis. 19/30 (63%) patients with dosimetric benefit completed their RT with DIBH. CONCLUSIONS: Despite a strong correlation between patient-related and dosimetric parameters, we cannot use the anatomical characteristics' thresholds to select patients for whom DIBH-RT will not be considered.

Outcome of treatment of recurrent glioblastoma multiforme in elderly and/or frail patients.

Optimal treatment of recurrent glioblastoma multiforme (rGBM) in elderly and/or frail patients remains virtually unexplored, the best supportive care (BSC) only is routinely administered due to the fatal prognosis. We evaluated the impact of different treatment methods on post-progression survival (PPS) and overall survival (OS) of such patients. Data from 98 elderly and/or frail rGBM patients, treated initially with 1-week or 3-week radiotherapy (RT) within the phase III IAEA study (2010-2013), were analyzed. KPS at relapse and salvage treatment methods were recorded. Kaplan-Meier method was used to estimate PPS and OS for different treatment modalities. Eighty-four patients experienced recurrence: 47 (56%) received BSC, 21 (25%)-chemotherapy (CHT), 8 (9.5%)-surgery, 3 (3.5%)-RT, for 5 (6%) the data was unavailable. Median OS from randomization for all 84 patients was 35 weeks: 55 versus 30 weeks for any treatment versus BSC, p < 0.0001. Median PPS was 15 weeks: 23 weeks with any treatment versus 9 weeks with BSC, p < 0.0001. For local treatment (surgery and/or RT) median PPS was 51 versus 21 weeks for CHT, p = 0.36. In patients with poor KPS (≤60) at relapse median PPS was 9 weeks with BSC versus 21 weeks with any treatment, p = 0.014. In poor KPS patients median PPS for local treatment was 14 weeks versus 21 weeks with CHT, p = 0.88. An active therapeutic approach may be beneficial for selected elderly and/or frail rGBM patients. Poor KPS patients may also benefit from active treatment, but there is no benefit of local treatment over CHT.

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.

Accelerated hypofractionated thoracic radiotherapy in limited disease small cell lung cancer : comparison with the results of conventionally fractionated radiotherapy.

PURPOSE: To compare accelerated hypofractionated (A-HYPO) radiotherapy (RT) with conventionally fractionated (CF) thoracic RT in patients with limited-disease small-cell lung cancer (LD-SCLC). METHODS: Out of 217 consecutive LD-SCLC patients, treated between 1997 and 2012, 82 received CF-RT (44-60 Gy, 2 Gy/ fraction) sequentially to 4-6 cycles of platinum-based chemotherapy (CHT), and 100 received A-HYPO-RT (42 Gy, 2.8 Gy/ fraction). Forty-two patients (42%) received "early" (before the 3rd cycle of CHT) A-HYPO-RT, and 58 (58%) patients received "late" A-HYPO-RT. Overall survival (OS), locoregional failure risk (LRFR) and toxicities were retrospectively evaluated and compared between CF-RT and A-HYPO-RT groups (also separately for "early" and "late" A-HYPO-RT). RESULTS: Median survival times (MST) for CF-RT and A-HYPO-RT were 18 and 24 months, respectively; 3-year OS were 19.1 and 39.4%, respectively (p=0.004). Three-year LRFR in CF-RT was 47.3% and 34.0% in the A-HYPO- RT group (p=0.12). Statistically significant difference in OS (p=0.007) and LRFR (p=0.03) was observed, favoring "early" A-HYPO-RT (MST=27 months, 3-year OS=40.0%, 3-year LRFR=28.4%) over CF-RT. Use of CF-RT (relative risk/RR=1.65, p=0.02) and poor CHT compliance (RR=1.69, p=0.03) were independent prognostic factors for poor OS; "early" start of RT was a favorable although non-significant prognostic factor for LRFR (RR=0.42, p=0.05). No difference in toxicities was observed between the groups. CONCLUSIONS: A-HYPO-RT results in better outcomes than CF-RT. "Early" A-HYPO-RT provides additional benefit in locoregional control and survival, without increased toxicity. These results indicate the need for a randomized study on the efficacy of A-HYPO-RT.

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.

HDR brachytherapy for the reirradiation of cervical and vaginal cancer: analysis of efficacy and dosage delivered to organs at risk.

OBJECTIVE: To evaluate the efficacy and toxicity of HDR brachytherapy (BT) for the reirradiation of cervical or vaginal cancer arising within a previously irradiated area with a special focus on dosage delivery to organs at risk. METHODS: Twenty consecutive patients with cervical (N = 19) or vaginal (N = 1) cancer were reirradiated with curative intent using BT with or without external beam irradiation and hyperthermia. The median biologically equivalent dose in 2 Gy fractions (EQD2), assuming α/ß = 10, for reirradiation was 48.8 Gy (range: 16.0-91.0 Gy), and the median cumulative EQD2 (for primary treatment and reirradiation) was 133.5 Gy (range: 96.8-164.2 Gy). The median follow-up after retreatment was 31 months (range: 6-86 months). RESULTS: The 3-year overall survival (OS) rate was 68% (95% confidence interval [CI]: 44%-91%). The 3-year disease-free survival (DFS) rate was 42% (95% CI: 19%-65%). The 3-year local control (LC) rate was 45% (95% CI: 22%-69%). For nine patients who received 3D treatment planning, the median cumulative EQD2 to 2 cm(3) of rectum was 94.4 Gy (range: 67.1-118.8 Gy) and to 2 cm(3) of bladder was 99.3 Gy (range: 70.4-122.3 Gy). Grade 3 late toxicity was observed in 3 patients (15%). An interval between primary RT and reirradiation of ≤ 12 months and a tumor diameter >3 cm were significant prognostic factors adversely affecting OS, DFS and LC. CONCLUSIONS: HDR BT is a valuable method for the reirradiation of cervical cancer. A cumulative EQD2 of approximately 100 Gy was safely delivered to 2 cm(3) of the bladder and the rectum.

Hypofractionated conformal radiotherapy in combination with chemotherapy in limited disease small cell lung cancer patients.

AIM: To evaluate the results of hypofractionated conformal radiotherapy (RT) in limited disease small cell lung cancer (LD-SCLC) patients, with particular interest in the value of "early" RT, i.e. given before the 3rd chemotherapy (CHT) cycle. MATERIAL AND METHODS: Outcome of hypofractionated RT (42 Gy, 2.8 Gy/fraction, given over 19-21 days, using "concomitant boost" technique - elective volume [39 Gy, 2.6 Gy/fraction] and tumour volumes treated during the same fraction) combined with CHT in 100 consecutive LD-SCLC patients, was retrospectively assessed. The outcomes were compared with a previously published series of 117 LD-SCLC patients treated in the same institution with hyperfractionated or conventionally fractionated RT. RESULTS: Forty-two patients (42%) received "early" RT. Grade 3 NCI CTC acute oesophageal toxicity appeared in 5% of patients. There were three treatment-related deaths. Three-year overall survival (OS) rate was 39.4%, median - 24 months in the examined group vs. 26.0%, and 18 months in historical control, P = 0.02. Three-year OS for 78 patients with completed CHT was 42.2%, median - 28 months vs. 30%, and 14 months for 22 patients who received ≤ 3 CHT cycles, (P = 0.03). The actuarial 3-year locoregional failure risk (LRFR) was 34.0% in the examined group vs. 51.0% in the historical control, P = 0.04. Multivariate analysis showed a marginally significant correlation between the "early" use of RT and LRFR: RR = 0.43 (95% CI: 0.17-1.04), P = 0.06, with no significant impact on OS. CONCLUSIONS: Shorter duration of RT using hypofractionation results in encouraging outcomes and acceptable toxicity. Completion of all planned CHT cycles is the most important factor for OS.

Palliative Thoracic Radiotherapy in the Era of Modern Cancer Care for NSCLC.

Palliative thoracic radiotherapy provides rapid and effective symptom relief in approximately two-thirds of NSCLC patients treated. In patients with poor performance status, the degree of palliation appears unrelated to the radiation dose or fractionation schedule. Conversely, in patients with good performance status, higher radiation doses administered over longer periods have shown modest survival benefits. These findings stem from studies conducted before the advent of immunotherapy and targeted therapy in clinical practice. Currently, there are no large prospective studies specifically dedicated to palliative radiotherapy conducted in this new treatment era. Modern radiotherapy technologies are now widely available and are increasingly used for palliative purposes in selected patients, reflecting the expanded array of therapeutic options for disseminated NSCLC and improved prognosis. Some traditional tenets of palliative thoracic radiotherapy, such as the improvement of overall survival with a protracted radiation schedule and the use of simple, cost-effective radiation techniques for palliative purposes, may no longer hold true for patients receiving immunotherapy or targeted therapy. The application of IMRT or SBRT in the context of palliative radiotherapy for NSCLC is not yet sufficiently explored, and this is addressed in this review. Moreover, new risks associated with combining palliative radiotherapy with these systemic treatments are being explored and are discussed within the context of palliative care. The optimal timing, doses, fractionation schedules, and treatment volumes for radiotherapy combined with immunotherapy or targeted therapy are currently subjects of investigation. In emergencies, radiotherapy should be used as a life-saving measure without delay. However, for other indications of palliative thoracic radiotherapy, decisions regarding doses, timing relative to systemic treatments, and treatment volumes should be made in a multidisciplinary context, considering the patient's prognosis, anticipated outcomes, and access to potentially effective treatments. We still lack robust data from prospective studies on this matter. This review examines and discusses available evidence on the use of palliative thoracic radiotherapy within the framework of modern treatment strategies for NSCLC.

Definitive radical external beam radiotherapy for rectal cancer: evaluation of local effectiveness and risk of late small bowel damage.

AIM: To present a retrospective analysis of results of definitive radiotherapy for rectal cancer. MATERIAL AND METHODS: Forty-one consecutive patients with rectal cancer (32% primary, 61% pelvic recurrence and 7% after R2 resection) who could not be treated with surgery underwent external beam radiotherapy. A median tumour dose of 64 Gy was given with 1.8-2.5 Gy per fraction using 2D or 3D technique. In 46% of patients, concurrent 5-Fu-based chemotherapy was given. The median follow-up was 54 months. RESULTS: Clinical complete response was achieved in 39% of patients. Five-year cumulative incidence of local failure, overall survival and cancer specific survival were 76%, 26% and 30%, respectively. Of 11 patients with local control, in five cases the tumour was larger than 5 cm and in the other five the tumour was fixed. Two patients, regarded as locally controlled had non-progressive tumour without local symptoms at the last follow-up of 54 and 118 months post-radiotherapy. Late toxicity occurred in 22% of patients, all with acceptable severity. There was no bowel obstruction requiring surgery despite that in 18 patients the small bowel dose was >60 Gy to a mean volume of 51 cm(3). CONCLUSION: Definitive radio(chemo)therapy provides a chance for local control even in patients with large fixed or recurrent rectal cancer.

[Outcome after PET-CT based radiotherapy for non-small cell lung cancer]. / Wyniki radioterapii planowanej na podstawie badania PET-CTu chorych na niedrobnokomórkowego raka pluca

INTRODUCTION: The value of PET-CT in radiotherapy for non-small cell lung cancer (NSCLC) with regard to determination of target volumes is established. It is less clear whether its use can improve clinical outcomes of irradiated NSCLC patients compared to conventional staging. The outcome of NSCLC patients included in a previously published prospective study of the value of PET-CT in curative radiotherapy candidates was assessed. MATERIALS AND METHODS: Patients were treated according to the PET-CT findings. The survival data were compared between 67 patients treated curatively and 22 patients with palliative treatment given after upstaging based on the PET-CT findings. Survival of curatively treated stage III patients was compared with a previously published outcome of 173 stage III patients treated in the same institution with the same radiation schedule but without PET-CT. RESULTS: The 3-year overall survival was 42% and 0% (median: 21 months and 7 months), for curatively and palliatively managed patients, respectively (p 〈 0.0001). However, the median overall survival of 17 months for 50 stage III patients was the same as that in a previously published series of stage III patients treated with the same radiation schedule but without PET-CT. Three-year overall survival rates were 33% for the PET-CT group and 19% for historical group, p = 0.1. Twenty-one local recurrences and 21 distant metastases were reported. Three of 50 patients (6%) treated without elective nodal irradiation developed isolated nodal failure (without local recurrence). CONCLUSIONS: The high early mortality rate in the patients disqualified from curative radiotherapy after PET-CT suggests the potential value of PET-CT for improving the radiotherapy outcome. However, this benefit seems to be limited in stage III patients.

Re-Whole Brain Radiotherapy for Brain Metastases: How to Evaluate an Outcome of Repeat Treatment When Its First Use Is Debatable.

Recently, a review on a pertinent issue of repeat whole-brain radiotherapy (re-WBRT) for recurring brain metastases was published [...].

Palliative extracranial radiotherapy in patients receiving immunotherapy for non-small cell lung cancer: a narrative review.

Background and Objective: Role of radiotherapy (RT) in the era of immuno-oncology (IO) in advanced non-small cell lung cancer (NSCLC) is rapidly changing. RT is not only intended for addressing palliation symptoms but also is considered as a potential tool potentializing an immunogenic effect of given drugs. However, the best timing, techniques, doses, volumes, and its use for asymptomatic patients is a subject of research. We performed a review on the role of palliative RT schedules in combination with IO for advanced NSCLC. Indications in symptomatic and asymptomatic patients, outcomes, toxicity, and possible developments are discussed. Methods: A literature search was conducted in MEDLINE and PubMed databases and clinicaltrials.gov using the keywords 'lung cancer' AND "immunotherapy" AND 'radiotherapy' OR "palliative radiotherapy". Key Content and Findings: Body of evidence indicate that palliative RT used in combination with IO is effective in terms of symptom management and safe; does not increase the risk of serious side effects, including serious pulmonary toxicity. We have limited data evidencing improvement of survival by addition of short ablative RT dose to one site of the disease to IO in oligometastatic NSCLC. Some data indicate that short ablative doses of stereotactic body radiation therapy (SBRT) are more effective with regard to treatment response and survival than protracted RT schedule with lower fractional doses. However, this may be a selection bias of better prognostic patients who underwent SBRT. The use of steroids being a potential concern during IO should not be prohibited if clinically indicated during palliative RT. Its detrimental effect shown in some studies may also be a result of selection bias, because steroids given for not cancer-related causes during IO did not decrease survival. Conclusions: RT for symptom management may be used during, directly before or after IO. This has a potential to ease symptom burdens and improve performance status (PS). However, still more studies are needed to establish optimal guidelines in asymptomatic patients for appropriate timing, volumes, dose, and fractionation schedules of palliative RT use in combination with IO.

Dosimetric comparison of three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, and volumetric-modulated arc therapy for free-breathing whole-breast irradiation: A planning study.

Background: Currently, recommended heart dose constraints are difficult to meet in whole-breast irradiation (WBI) for left-sided breast cancer patients, who cannot be treated with the deep inspiration breath hold. We performed a radiotherapy planning study to establish if the use of intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) allows for better sparing of the heart and its subvolumes than the three-dimensional conformal radiation therapy (3D-CRT), and how these attempts affect the dose delivered to the other organs. Methods: A total of 17 left-sided and 10 right-sided consecutive patients treated with free-breathing WBI were retrospectively included. The 3D-CRT, IMRT, and VMAT plans were generated. Several dose-volume parameters and plan quality indices were compared, separately for the left- and right-sided plans. Results: All the techniques fulfilled the planning objectives. In the left-sided plans, there was no heart or left ventricle dose reduction with IMRT, nor with VMAT; the maximum dose in the left anterior descending coronary artery was reduced with VMAT (P = 0.005); V5 for the contralateral breast, contralateral lung, and total-body increased markedly in VMAT, and for the ipsilateral lung (V5IL) also in IMRT, compared with 3D-CRT (P < 0.001). In the right-sided plans, the V5 values, except for V5IL, did not differ between the three techniques. Conclusions: IMRT and VMAT had a limited heart-sparing benefit in the left-sided free-breathing WBI, at the cost of increased low-dose volumes, measured by V5. The low-dose volumes are not increased by IMRT or VMAT in the right-sided WBI, where heart sparing is not a problem, but the attempts to reduce cardiac doses in the left-sided WBI increase them.

Five-year follow-up after stereotactic body radiotherapy for medically inoperable early-stage non-small cell lung cancer: a multicenter study.

Background: Stereotactic body radiotherapy (SBRT) has proven to provide high rates of tumor control for patients with early-stage non-small cell lung cancer (NSCLC). We are reporting a multicenter experience of long-term clinical outcomes and adverse effect profiles of patients with medically inoperable early-stage NSCLC treated with SBRT. Methods: A total of 145 early-stage NSCLC patients underwent SBRT at the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Shandong Cancer Hospital and Institute, and Shanghai Pulmonary Hospital between October 2012 and March 2019. Four-dimensional computed tomography (4D-CT) simulation was used for all patients. All received a biologically effective dose (BED; α/ß=10) of 96-120 Gy with the prescribed isodose line covering >95% of the planning target volume (PTV). Survival was analyzed by the Kaplan-Meier method. Survival was estimated using the Kaplan-Meier method. Results: The median tumor diameter was 2.2 (range, 0.5-5.2) cm. The median follow-up was of 65.6 months. Thirty-five patients (24.1%) developed disease recurrence. The rates of local, regional, and distant disease recurrence were, respectively, 5.1%, 7.4%, and 13.2% at 3 years; and 9.6%, 9.8%, and 15.8% at 5 years. Progression-free survival (PFS) rates at 3 and 5 years were 69.2% and 60.5% respectively; the overall survival (OS) rates were 78.1% and 70.1%, respectively. Five patients (3.4%) experienced grade 3 treatment-related adverse events (AEs). No patient experienced grade 4 or 5 toxicity. Conclusions: From our retrospective analysis with long-term follow-up in Chinese population, SBRT achieved high rate of local control (LC) and low toxicity in patients with early-stage NSCLC. This study offered robust long-term outcome data of SBRT in the Chinese population, which was very rarely reported in China before.

Contouring cardiac substructures on average intensity projection 4D-CT for lung cancer radiotherapy: A proposal of a heart valve contouring atlas.

BACKGROUND AND PURPOSE: A detailed contouring atlas of the heart valves is lacking. Existing heart contouring atlases have not been evaluated on average intensity projection four-dimensional non-contrast computed tomography (AVE-4D-CT) scans, routinely used for organ-at-risk delineation in lung cancer radiotherapy. We aimed to develop the heart valve contouring atlas and to assess inter-observer variation in delineation of the heart, its substructures, and coronary arteries on AVE-4D-CT scans, along with its impact on radiotherapy doses. MATERIALS AND METHODS: A heart valve contouring atlas was developed. Five radiation oncologists and four cardiologists delineated the valves according to this atlas, and the remaining heart substructures according to the existing atlases, on AVE-4D-CT scans of ten patients who underwent radio(chemo)therapy for NSCLC. The observer contours were then compared to the collectively defined "reference" contours. Spatial variation was assessed using the Sørensen-Dice similarity coefficient (DSC), directed average Hausdorff distance (DAH), directed Hausdorff distance (HD), and the mean distance to agreement (MDA). The effect of spatial variation on radiotherapy doses was assessed using the patients' treatment plans. RESULTS: Inter-observer contour overlap (mean DSC) was 0.68, 0.49, 0.45 and 0.45, and inter-observer contour separation (mean DAH) was 2.1, 3.4, 2.6 and 2.9 mm for the pulmonic (PV), aortic (AV), mitral (MV) and tricuspid valve (TV), respectively. Mean HD was higher for TV and MV (13.3 and 11.7 mm) than for AV and PV (7.8 and 7 mm). The highest mean MDA of 3.1 mm was found for AV, and the lowest (1.9 mm) for PV. Inter-observer agreement was the lowest for the coronary arteries, but statistically significant dose variation was found mainly in the left ventricular septal and anterior segments. CONCLUSION: Our atlas enables reproducible delineation of the heart valves. Delineation of the heart and its substructures on AVE-4D-CT scans is feasible, with inter-observer variability similar to that reported on conventional non-contrast CT scans.

A nomogram to predict the recurrence-free survival and analyze the utility of chemotherapy in stage IB non-small cell lung cancer.

BACKGROUND: Large part of patients of stage IB non-small cell lung cancer (IB NSCLC) may suffer recurrence after surgery. This study is to determine risk factors and establish a nomogram for postoperative recurrence and to provide a reference for adjuvant chemotherapy selection in patients with stage IB NSCLC. METHODS: A total of 394 patients with postoperative stage IB NSCLC who visited Fujian Medical University Union Hospital between January 2010 and June 2016 were selected. Patients were divided into training and validation cohorts based on the time of diagnosis. Independent risk factors were identified using a Cox proportional hazards regression model. A nomogram was created to predict recurrence-free survival (RFS) and was validated with an independent cohort. The predictive ability of the nomogram was evaluated using the concordance index (C-index) and calibration curve. RFS between the high- and low-risk groups was determined using Kaplan-Meier curves, and subgroup analysis of chemotherapy was performed. RESULTS: Visceral pleura invasion, micropapillary structures, tumor size, preoperative serum carcinoembryonic antigen (CEA) level, preoperative serum cytokeratin-19 fragments (Cyfra21-1) level, and postoperative histology were identified as independent risk factors for stage IB NSCLC recurrence. Discrimination of the nomogram showed good prognostic accuracy and clinical applicability, with a C-index of 0.827 and 0.866 in the training and validation cohorts, respectively. The difference in RFS between the high- and low-risk groups in both cohorts was significant (P<0.05). Finally, a significant difference was observed on whether high-risk group should accept postoperative chemotherapy (P<0.05). CONCLUSIONS: This nomogram can predict postoperative recurrence probability in patients with stage IB NSCLC, and can select patients with risk factors who need adjuvant chemotherapy.

International consensus on radiotherapy in metastatic non-small cell lung cancer.

Background: Lung cancer is the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) accounting for most cases. While radiotherapy has historically served as a palliative modality in metastatic NSCLC, considerable advances in its technology and the continuous development of cutting-edge therapeutic agents, such as targeted therapy and immune checkpoint inhibitors (ICIs), are increasing its role in the multi-disciplinary management of the disease. Methods: International radiotherapy experts were convened to consider and reach consensuses on the clinical utilities of radiotherapy in metastatic NSCLC, with the aim to provide patient-focused, up to date, evidence-based, recommendations to assist cancer specialists in the management of patients with metastatic NSCLC worldwide. Results: Timely radiotherapy can offer rapid symptom alleviation and allow subsequent aggressive treatment approaches in patients with heavy tumor burden and/or oncologic emergencies. In addition, appropriate incorporation of radiotherapy as concurrent, consolidation, or salvage therapy makes it possible to achieve long-term survival, or even cure, for patients with oligo-metastatic disease. Cranial radiotherapy plays an important role in the management of brain metastasis, potentially augmenting the response and prolonging survival associated with targeted agents and ICIs. However, key questions remain, such as the appropriate choice of radiation techniques, optimal sequence of systemic therapies and radiotherapy, and optimal patient selection for such combination strategies. Although a strong rationale for combining radiotherapy and ICIs exists, its optimal parameters in this setting remain to be established. Conclusions: In the modern era, radiotherapy serves not only as a palliative tool in metastatic NSCLC, but also plays active roles in patients with oligo-focal disease, CNS metastasis and receiving ICIs.

[Outcome of three-dimensional conformal radiotherapy for early stage non-small cell lung cancer patients who met or not inclusion criteria for stereotactic-body radiation therapy]. / Wyniki konformalnej radioterapii chorych na niedrobnokomórkowego raka pluca we wczesnym stopniu zaawansowania spelniajacych kryteria oraz niespelniajacych kryteriów kwalifikacji do napromieniania stereotaktycznego.

INTRODUCTION: In early stage non-small cell lung cancer (NSCLC) the stereotactic body radiation therapy (SBRT) gives promising results, similar to the results of surgical series. However, not all such patients are the candidates for this treatment method. The retrospective analysis of the results of three-dimensional conformal radiotherapy (3D-CRT) in stage I and II of NSCLC was undertaken, with a special focus on the patients who were candidates for SBRT treatment, but received 3D-CRT due to no access to the SBRT. MATERIAL AND METHODS: One hundred thirty-two consecutive stage I-II NSCLC patients who received radical 3D-CRT between 1998 and 2009 were included. Different radiotherapy schedules were used; thus the biologically equivalent doses (BED) were calculated for all. Sixty-eight patients met criteria of qualification for SBRT (peripheral T1-3N0 tumors with diameter £ 5 cm). Overall survival and local progression free survival (LPFS) were estimated for the whole group and compared for patients being and not being candidates for SBRT. Uni- and multivariate analyses were performed for prognostic factors. RESULTS: Median BED value was 74 Gy (58-82 Gy). Patients who met SBRT criteria had significantly smaller gross tumor volume (GTV) comparing to the remainder (p 〈 0.00001). Three-year overall and local progression free survival rates were 37% and 50%, respectively. In comparison of SBRT candidates and others, only significant difference in three-year LPFS was obtained, 58% and 35%, respectively, p = 0.04. However, in the multivariate analysis, GTV, performance status, and stage were the only three prognostic factors for LPFS. CONCLUSIONS: After 3D-CRT, superior local control for early stage NSCLC patients who met criteria of inclusion for SBRT in comparison with the remainder was demonstrated. However, this outcome was inferior to the local control after SBRT reported in the literature.