Is the time interval between surgery and radiotherapy important in operable nonsmall cell lung cancer? A retrospective analysis of 340 cases☆

This study aimed to assess the shifting patterns of the mediastinum, including the target volume and the isocenter point during the postoperative radiotherapy (PORT) process of non-small cell lung cancer (NSCLC), and to observe the occurrence of radiation injury. Additionally, we investigated the significance of mid-term assessment during the implementation of the PORT process.

We established coordinate axes based on bone anatomy and measured the mediastinum's three-dimensional direction and the shift of the isocenter point's shift in the PORT process. Statistical analysis was performed using Wilcoxon, Kruskal-Wallis, and the Chi-square test. P < 0.05 was considered statistically significant.

In this study, the analysis of patients revealed that the shift of anterior and posterior mediastinum (X), left and right mediastinum (Y), upper and lower mediastinum (Z), anterior and posterior isocenter point (X_i), and the left and right isocenter points (Y_i) in the PORT process were 0.04–0.53, 0.00–0.84, 0.00–1.27, 0.01–0.86, and 0.00–0.66 cm, respectively. The shift distance of the mediastinum was Z > Y > X, and the shift distance of the isocenter point was X_i > Y_i. According to the ROC curve, the cut-off values were 0.263, 0.352, 0.405, 0.238, and 0.258, respectively, which were more significant than the cut-off values in 25 cases (25%), 30 cases (30%), 30 cases (30%), 17 cases (17%), and 15 cases (15%). In addition, there was a significant difference in the shift of the mediastinum and the isocenter point (all P = 0.00). Kruskal-Wallis test showed no statistically significant difference between mediastinal shift and resection site in X, Y, and Z directions (P = 0.355, P = 0.239, P = 0.256), surgical method (P = 0.241, P = 0.110, P = 0.064). There was no significant difference in the incidence of RE and RP in PORT patients (P > 0.05). No III–IV RP occurred. However, the incidence of ≥ grade III RE in the modified plan cases after M-S was significantly lower than in the original PORT patients, 0% and 7%, respectively (P = 0.000).

In conclusion, this study provides evidence that mediastinal shift is a potential complication during the PORT process for patients with N2 stage or R1–2 resection following radical resection of NSCLC. This shift affects about 20–30% of patients, manifesting as actual radiation damage to normal tissue and reducing the local control rate. Therefore, mid-term repositioning of the PORT and revision of the target volume and radiation therapy plan can aid in maintaining QA and QC during the treatment of NSCLC patients and may result in improved patient outcomes.

Cette étude visait à évaluer les variations du médiastin, y compris le volume cible et l’isocentre, pendant la radiothérapie postopératoire du cancer du poumon non à petites cellules, et à observer la survenue de lésions dues aux rayonnements.

Nous avons établi des axes de coordonnées en fonction de l’anatomie osseuse et mesuré la direction tridimensionnelle du médiastin et le déplacement du point d’isocentre. L’analyse statistique a été effectuée à l’aide des tests de Wilcoxon, de Kruskal-Wallis et du X². p < 0,05 a été considéré comme statistiquement significatif.

L’analyse a révélé que le déplacement du médiastin en avant et en arrière (X), à gauche et à droite (Y), en haut et en bas (Z), de l’isocentre en avant et en arrière (X_i) et à gauche et à droite (Y_i) était respectivement de 0,04–0,53, 0,00–0,84, 0,00–1,27, 0,01–0,86 et 0,00–0,66 cm. Le déplacement du médiastin était Z > Y > X, Le déplacement de l’isocentre était X_i > Y_i. Selon la courbe ROC (receiver operating characteristic), les valeurs de cut off étaient respectivement de 0,263, 0,352, 0,405, 0,238 et 0,258, plus significatives que les valeurs limites dans 25 cas (25 %), 30 cas (30 %), 30 cas (30 %) 17 cas (17 %), et 15 cas (15 %). Selon la courbe ROC de plus, il y avait une différence significative dans le déplacement du médiastin et de l’isocentre (tous p = 0,00). Le test de Kruskal-Wallis n’a montré aucune différence statistiquement significative entre le déplacement du médiastin et le site de résection dans les directions X, Y et Z (p = 0,355, p = 0,239, p = 0,256), et la méthode chirurgicale (p = 0,241, p = 0,110, p = 0,064). Il n’y avait aucune différence significative dans l’incidence des œsophagites et des pneumonites (p > 0,05). Il n’y a pas eu de pneumonite de grade III–IV. Cependant, l’incidence des œsophagites de grade ≥ III dans les cas du plan modifié après le déplacement médiastinal était significativement plus faible, 0 % contre 7 % (p = 0000).

En conclusion, cette étude fournit des preuves que le déplacement médiastinal est une source de complication potentielle de la radiothérapie après résection N2 ou R1–2. Ce changement affecte environ 20 à 30 % des patients, se manifestant par des dommages réels dans les tissus normaux et une réduction du taux de contrôle local. Par conséquent, le repositionnement à mi-parcours de la radiothérapie postopératoire et la révision du volume cible et du plan de radiothérapie peuvent aider à maintenir l’assurance et le contrôle de la qualité.

The purpose of the current study was to retrospectively assess the effect of postoperative radiotherapy (RT) delay on survival for patients with esophageal cancer. From 2008 to 2011, patients with esophageal cancer who had undergone postoperative RT in five different hospitals in China were reviewed. Clinical data, including time interval between surgery to RT, were prospectively collected. Kaplan-Meier method was conducted to estimate the effect of each variable on progression-free survival (PFS) and overall survival (OS), with differences assessed by log-rank test. Univariate Cox proportional-hazards models were performed for both PFS and OS for all assumed predictor variables. Statistically significant predictor variables (P < .05) on univariate analysis were then included in multivariate Cox proportional-hazards models, which were performed to compare the effects of RT delay on PFS and OS. A total of 316 patients were finally enrolled in this prospectively multicentric study. Time to RT after surgery varied from 12 days to over 60 days (median, 26 days). Multivariate analysis showed that delay to RT longer than the median does not appear to be a survival cost. There was also no statistically difference in PFS (P = .513) or OS (P = .236) between patients stratified by quartiles (≤21 days vs ≧35 days). However, patients with particularly long delays (≧42 days) demonstrated a detrimental impact on OS (P = .021) but not PFS (P = .580). Delaying postoperative RT of esophageal cancer does not impact PFS, but results in a significant reduction on OS if delaying longer than 6 weeks.

Current guidelines recommend postoperative radiation therapy (PORT) for incompletely resected non-small cell lung cancer (NSCLC). However, there is still a paucity of evidence for this approach. Hence, we analyzed survival in 78 patients following radiotherapy for incompletely resected NSCLC (R1) and investigated prognostic factors.

All 78 patients with incompletely resected NSCLC (R1) received PORT between December 2001 and September 2014. The median total dose for PORT was 60 Gy (range 44–68 Gy). The majority of patients had locally advanced tumor stages (stage IIA (2.6%), stage IIB (19.2%), stage IIIA (57.7%) and stage IIIB (20.5%)). 21 patients (25%) received postoperative chemotherapy.

Median follow-up after radiotherapy was 17.7 months. Three-year overall (OS), progression-free (PFS), local (LPFS) and distant progression-free survival (DPFS) rates were 34.1, 29.1, 44.9 and 51.9%, respectively. OS was significantly prolonged at lower nodal status (pN0/1) and following dose-escalated PORT with total radiation doses >54 Gy (p = 0.012, p = 0.013). Furthermore, radiation doses >54 Gy significantly improved PFS, LPFS and DPFS (p = 0.005; p = 0.050, p = 0.022). Interestingly, survival was neither significantly influenced by R1 localization nor by extent (localized vs. diffuse). Multivariate analyses revealed lower nodal status and radiation doses >54.0 Gy as the only independent prognostic factors for OS (p = 0.021, p = 0.036).

For incompletely resected NSCLC, PORT is used for improving local tumor control. Local progression is still the major pattern of failure. Radiation doses >54 Gy seem to support improved local control and were associated with better OS in this retrospective study.

L’objectif était la rédaction d’un document pratique destiné aux radiothérapeutes et aux radiophysiciens décrivant la technique d’irradiation d’un cancer bronchique non à petites cellules. Les bonnes pratiques concernent la prise en charge de patients atteints de cancer bronchique localisé au thorax et inopérables ou devant bénéficier d’une irradiation postopératoire. Le document a été développé selon une méthodologie visant à intégrer les données actuelles de la science à partir d’une analyse de la littérature sur le sujet et l’expertise de radiothérapeutes, radiophysiciens, pneumologues et méthodologistes de la région Rhône-Alpes. À partir des étapes nécessaires au bon déroulement d’une radiothérapie, les rédacteurs de ce document ont proposé des définitions communes concernant le centrage et le repérage de la zone à traiter, le calcul de la distribution de la dose, la préparation du patient au traitement, le traitement et la surveillance pendant le traitement. Les recommandations de ce guide ont pris en compte les particularités liées à la nature de la région traitée et plus particulièrement l’hétérogénéité pulmonaire, les mouvements respiratoires et la radiosensibilité du tissu pulmonaire sain. Même si l’aspect technique de la radiothérapie a été particulièrement développé, l’intérêt accordé à l’information du patient revêt toute son importance pour une prise en charge thérapeutique de qualité. Les auteurs du document ont souhaité que ce guide des bonnes pratiques, qui sera actualisé régulièrement, aide les radiothérapeutes et leur permette d’harmoniser leurs pratiques.

The objective was the drafting of a practical document intended for radiotherapists and radiophysicists, describing the technique of irradiation of a non small cell bronchial cancer. The good practices concern the care of patients affected by bronchial cancer localized in the thorax and inoperable or patients who must undergo postoperative irradiation. The document has been developed according to a methodology aiming to join the current scientific data from an analysis of the literature on the subject and the assessment of radiotherapists, radiophysicists, lung specialists and methodologists from Rhône-Alpes area. From the stages necessary for the good progress of a radiotherapy, the writers of this document proposed common definitions concerning the centering and the location of the zone to be treated, the calculation of the dose distribution, the preparation of the patient for the treatment, the treatment and the surveillance during the treatment. The recommendations of this guide took into account the peculiarities bound to the nature of the treated region and more particularly the lung heterogeneity, respiratory movements and the radiosensibility of healthy lung tissue. Even if the technical aspect of the radiotherapy was particularly developed, the interest accorded to patient information takes on all its importance for a therapeutic coverage of quality. The authors of the document wished that this Guide of Good Practices, which will be regularly updated, helps the radiotherapists and allows them to harmonize their practices.

To synthesize the direct clinical evidence relating waiting times (WTs) for radiotherapy (RT) to the outcomes of RT.

We did a systematic review of the literature between 1975 and 2005 to identify clinical studies describing the relationship between WTs and outcomes of RT. Only high quality (HQ) studies that had adequately controlled for confounding factors were included in the primary analysis. WTs that had originally been reported as a categorical variable were converted to a continuous variable based on the distribution of WTs in each category. Meta-analyses were done using a fixed-effect model.

The systematic review identified 44 relevant studies. Meta-analyses of 20 HQ studies of local control demonstrated a significant increase in the risk of local failure with increasing WT, RR_{local recurrence/month} = 1.14, 95% Confidence Intervals (CI): 1.09–1.21. For post-operative RT for breast cancer; RR_{local recurrence/month} = 1.11, 95%CI: 1.04–1.19. For post-operative RT for head and neck cancer, RR_{local recurrenc/month} = 1.28, 95%CI: 1.08–1.52. For definitive RT for head and neck cancer, RR_{local recurrence/month} = 1.15, 95%CI: 1.02–1.29.

There was little evidence of any association between WTs and the risk of distant metastasis. Meta-analyses of the 6 HQ studies of breast cancer showed RR_{metastasis/month} = 1.04, 95%CI: 0.98–1.09. Meta-analyses of 4 HQ studies of breast cancer showed no significant decrease in survival with increasing WT, RR_death/month = 1.06, 95%CI: 0.97–1.16, but there was a marginally significant decrease in survival in 4 HQ studies of head and neck cancer, RR_death/month = 1.16, 95%CI: 1.02–1.32.

The risk of local recurrence increases with increasing WTs for RT. The increase in local recurrence rate may translate into decreased survival in some clinical situations. WTs for RT should be as short as reasonably achievable.

Surgery alone can cure 40–85% of patients with localized non-small cell lung cancer, depending on tumor stage and metastastic lymph-node involvement. As local failure rates occur in up to 50% of the cases, postoperative radiotherapy as an adjuvant treatment option has been evaluated in several trials. This review brielfly summarizes the published data mainly from randomized trials. While most of the studies showed a decrease in local recurrence rate, especially in stage-III/N2 tumors after postoperative radiotherapy, no impact could be shown on overall survival. In early stages a detrimental effect of postoperative radiotherapy has been postulated, but those findings have to be interpreted with caution as radiation techniques used were suboptimal and probably not today's state of the art. A carefully designed randomized trial using modern radiotherapy techniques is warrented to define the impact of irradiation on completely resected NSCLC.