Health-related quality of life after prophylactic cranial irradiation for stage III non-small cell lung cancer patients: Results from the NVALT-11/DLCRG-02 phase III study.

BACKGROUND AND PURPOSE: The NVALT-11/DLCRG-02 phase III trial (clinicaltrials.gov identifier: NCT01282437) showed that, after standard curative intent treatment, prophylactic cranial irradiation (PCI) decreased the incidence of symptomatic brain metastases (BM) in stage III non-small cell lung cancer (NSCLC) patients compared to observation. In this study we assessed the impact of PCI on health-related quality of life (HRQoL). In addition, an exploratory analysis was performed to assess the impact of neurocognitive symptoms and symptomatic BM on HRQoL. MATERIALS AND METHODS: Stage III NSCLC patients were randomized between PCI and observation. HRQoL was measured using the EuroQol 5D (EQ-5D-3L), EORTC QLQ-C30 and QLQ-BN20 instruments at completion of standard curative intent treatment and 4 weeks, 3, 6, 12, 24 and 36 months thereafter. Generalized linear mixed effects (GLM) models were used to assess the impact of PCI compared to observation over time on three HRQoL metrics: the EORTC QLQ-C30 global health status and the EQ-5D-3L utility and visual analogue scale (EQ VAS) scores. RESULTS: In total, 86 and 88 patients were included in the PCI and observation arm, with a median follow-up of 48.5 months (95% CI 39-54 months). Baseline mean HRQoL scores were comparable between the PCI and observation arm for the three HRQoL metrics. In the GLM models, none of the HRQoL metrics were clinically relevant or statistically significantly different between the PCI and the observation arm (p-values ranged between 0.641 and 0.914). CONCLUSION: No statistically significant nor a clinically relevant impact of PCI on HRQoL was observed.

[Treatment of patients with stage III non-small cell lung cancer: concurrent high-dose chemotherapy and radiotherapy]. / Behandeling van patiënten met niet-kleincellig longcarcinoom stadium III: gelijktijdig hooggedoseerde chemotherapie en radiotherapie.

The treatment of patients with locally advanced non-small cell lung cancer (stage III) has changed significantly in the past few years. Patients with a non-resectable stage IIIA/B tumour are given combined treatment consisting ofchemotherapy and radiotherapy. These can be administered sequentially or concurrently. It has been shown recently that concurrent chemoradiotherapy gives a survival advantage in comparison with sequential chemoradiotherapy. Cisplatin and etoposide are usually the drugs of choice for chemotherapy in patients with stage III cancer. A biologically effective dose of radiotherapy equivalent to 60-66 Gy, over a maximum of 6.5 weeks, should be given. Surgery is possible for a selected group of patients, provided a complete objective mediastinal response has been achieved after chemoradiotherapy and a complete resection appears to be technically feasible. It is recommended to apply this treatment in a research setting. High-dose concurrent chemoradiotherapy is advised as the standard treatment for stage III non-small cell lung cancer in patients in good physical condition.

Sequential versus concurrent chemo-radiotherapy in inoperable stage III non-small cell lung cancer.

AIM: To define the best sequence of radiotherapy and chemotherapy for inoperable stage III non-small cell lung (NSCL) tumours. MATERIALS AND METHODS: A systematic review was performed on the clinical results of radiotherapy, combined or not with chemotherapy, for inoperable NSCL cancer stage III. The mean median survival time (MST) and mean overall survival (OS) percentages were derived for radiotherapy only, for sequential and for concurrent chemo-radiotherapy. RESULTS: The mean median survival duration +/- standard deviation for radiotherapy only was 10.4 +/- 1.8 months. For sequential chemo- and radiotherapy it was increased to 13.0 +/- 1.2 months. When radiotherapy in the sequential regimen was accompanied by chemotherapy, the mean median duration was 15.8 +/- 2.6 months. For concurrent radio-chemotherapy it was further increased to 16.4 +/- 2.7 months. The mean 2- and 3-year overall survivals for radiotherapy alone, sequential and concurrent radio-chemotherapy were 17.1 +/- 4.6 and 10, 23.8 +/- 6.3 and 18.5 +/- 7.0, and 32.5 +/- 8.7 and 25.7 +/- 6.3%, respectively. CONCLUSION: Concurrent chemo-radiotherapy demonstrated increased efficacy over sequential chemotherapy and radiotherapy and should be the treatment of choice. Further improvements may be obtained by optimising the conditions for concurrent chemo-radiotherapy.

Tumour control probability of stage III inoperable non-small cell lung tumours after sequential chemo-radiotherapy.

UNLABELLED: The aim of this study was to investigate the influence of the duration of waiting time between the end of induction chemotherapy and the start of radiotherapy on tumour control probability (TCP). PATIENTS AND METHODS: Twenty-three patients with inoperable stage III non-small cell lung cancer (NSCLC) received induction chemotherapy followed by radiotherapy. The mean waiting period between the end of induction chemotherapy and the start of radiotherapy was 80 days; in this period, the median tumour volume increased by a factor of about 6. The Poisson model for TCP and the linear-quadratic model were used to calculate changes in TCP in the waiting time. RESULTS: The 2-year survival of patients treated with curative intent was 8%, lower than the mean value of 26% derived from other studies. Assuming that radiotherapy started on the day of restaging or on the first day of radiotherapy (RT1), the calculated mean TCP at restaging was 13.3% and at RT1 was 0.5% for patients treated with curative intent. CONCLUSION: The calculated TCP decreased in the waiting period from 13.3 to less than 1%. Hence, the relatively long interval time between chemo- and radiotherapy had a deleterious effect on local control. We recommend the waiting time to be as short as possible.

Accelerated regrowth of non-small-cell lung tumours after induction chemotherapy.

Induction chemotherapy of non-small-cell lung cancer (NSCLC) stage III with gemcitabine and cisplatin for downstaging of the tumour with the aim for further treatment with ionising radiation is one of the treatments for lung cancer patients. The purpose of this study was to investigate the influence of the waiting time for radiotherapy, that is, the interval between induction chemotherapy and radiotherapy, on the rate of tumour growth for patients with NSCLC. Interval times between the end of induction chemotherapy and date of diagnostic CT, planning CT and first day of radiotherapy were determined for 23 patients with NSCLC. Increase in gross tumour volume was measured for 18 patients by measuring the dimensions of the primary tumour and lymph node metastases on the diagnostic CT after induction chemotherapy and on the CT used for radiotherapy planning. For each patient, the volume doubling time was calculated from the time interval between the two CTs and ratio of the gross volumes on planning CT and diagnostic CT. The mean time interval between end of chemotherapy and day of diagnostic CT was 16 days, and till first day of radiotherapy 80.3 (range 29-141) days. In all, 41% of potentially curable patients became incurable in the waiting period. The ratio of gross tumour volumes of the two CTs ranged from 1.1 to 81.8 and the tumour doubling times ranged from 8.3 to 171 days, with a mean value of 46 days and median value of 29 days. This is far less than the mean doubling time of NSCLC in untreated patients found in the literature. This study shows that in the time interval between the end of induction chemotherapy and the start of radiotherapy rapid tumour progression occurs as a result of accelerated tumour cell proliferation: mean tumour doubling times are much shorter than those in not treated tumours. As a consequence, the gain obtained with induction chemotherapy with regard to volume reduction was lost in the waiting time for radiotherapy. We recommend diminishing the time interval between chemo- and radiotherapy to as short as possible.

Benefits and side effects of lateral ovarian transposition (LOT) performed during radical hysterectomy and pelvic lymphadenectomy for early stage cervical cancer.

Ovarian function and ovarian cyst formation after radical hysterectomy and pelvic lymphadenectomy with lateral ovarian transposition (LOT) have been retrospectively examined in 54 patients with early stage cervical cancer (FIGO IB or IIA) with a follow-up of 3-7 years. Patients were divided into two groups: those without adjuvant pelvic radiotherapy (36 patients) and those with adjuvant pelvic radiotherapy (18 patients). Ninety-one percent (33/36) of the patients without adjuvant pelvic radiotherapy and 66% (12/18) of the patients with adjuvant pelvic radiotherapy remained without evidence of recurrent disease. Of the 36 patients who did not receive adjuvant pelvic radiotherapy, only two patients became postmenopausal (5.5%). However, of the 18 patients who also received adjuvant pelvic radiotherapy, 5 became postmenopausal (28%). There was a tendency to become postmenopausal if the scatter radiation dose at the transposed ovaries was 300 cGy or more, but our series is too small to allow a definite conclusion. This scatter radiation dose did not depend on the distance the ovaries were placed from the linea innominata, because of the variation in the level of the cranial border of the radiation field. Three out of 54 patients (5.5%) developed symptomatic ovarian cysts, of which 2 required surgical intervention because of pain symptoms. Remarkably, in one of them cyst formation occurred 5 years after surgery. Of the 3 patients with symptomatic ovarian cysts this was the only patient who received adjuvant pelvic radiotherapy. From these data it can be concluded that LOT protects ovarian function in most patients undergoing radical hysterectomy and pelvic lymphadenectomy for early stage cervical cancer, even if they receive adjuvant pelvic radiotherapy, with an acceptable risk of development of symptomatic ovarian cysts.

A unique case of intracranial metastasis from lung carcinoma.

We describe a case of an intracranial metastasis from a lung carcinoma in the same location from which an intracranial meningioma had been completely removed surgically eleven months earlier. It is demonstrated that the metastasis originated in the scar of the first operation.