Long-Term Follow-Up of Patients with Conjunctival Lymphoma after Individualized Lens-Sparing Electron Radiotherapy: Results from a Longitudinal Study.

Irradiation with electrons is the primary treatment regime for localized conjunctival low-grade lymphomas. However, radiation-induced cataracts are a major cause of treatment-related morbidity. This study investigates whether lens-sparing electron irradiation produces sufficient disease control rates while preventing cataract formation. All consecutive patients with strictly conjunctival, low-grade Ann Arbor stage IE lymphoma treated with superficial electron irradiation between 1999 and 2021 at our department were reviewed. A total of 56 patients with 65 treated eyes were enrolled with a median follow-up of 65 months. The median dose was 30.96 Gy. A lens-spearing technique featuring a hanging rod blocking the central beam axis was used in 89.2% of all cases. Cumulative incidences of 5- and 10-year infield recurrences were 4.3% and 14.6%, incidences of 5- and 10-year outfield progression were 10.4% and 13.4%. We used patients with involvement of retroorbital structures treated with whole-orbit photon irradiation without lens protection-of which we reported in a previous study-as a control group. The cumulative cataract incidence for patients treated with electrons and lens protection was significantly lower (p = 0.005) when compared to patients irradiated without lens protection. Thus, electrons are an effective treatment option for conjunctival low-grade lymphomas. The presented lens-sparing technique effectively prevents cataract formation.

MRI-based long-term follow-up of indolent orbital lymphomas after curative radiotherapy: imaging remission criteria and volumetric regression kinetics.

We systematically analyzed the kinetics of tumor regression, the impact of residual lesions on disease control and the applicability of the Lugano classification in follow-up MRI of orbital non-Hodgkin lymphomas that were irradiated with photons. We retrospectively analyzed a total of 154 pre- and post-irradiation MRI datasets of 36 patients with low-grade, Ann-Arbor stage I, orbital non-Hodgkin lymphomas. Patients with restricted conjunctival involvement were excluded. Lymphoma lesions were delineated and volumetrically analyzed on T1-weighted sequences. Tumor residues were present in 91.2% of all cases during the first six months after treatment. Volumetric partial response rates (> 50% volume reduction) were 75%, 69.2%, and 50% at 12-24 months, 36-48 months and > 48 months after the end of treatment. The corresponding complete response (CR) rates according to the Lugano classification were 20%, 23.1% and 50%. During a median clinical follow-up of 37 months no significant differences in progression free survival (PFS) rates were observed between the CR and non-CR group (p = 0.915). A residual tumor volume below 20% of the pretreatment volume should be expected at long-term follow-up beyond one year after radiotherapy.

Long-term follow-up and health-related quality of life among cancer survivors with stage IEA orbital-type lymphoma after external photon-beam radiotherapy: Results from a longitudinal study.

We assessed the long-term outcomes and treatment-related adverse effects of patients with Stage I, "orbital-type" lymphomas that were uniformly treated with photons. All consecutive patients diagnosed with low-grade, Ann Arbor Stage IEA orbital lymphoma treated between 1999 and 2020 at our department were retrospectively reviewed. We excluded patients with exclusive conjunctival involvement, typically treated with en face electrons. In order to quantify radiotherapy related side effects we applied the CTCAE criteria, analyzed changes in visual acuity, quantified dry eye symptoms by use of the Ocular Surface Disease Index (OSDI) score and applied the EORTC QLQ-C30 questionnaire for quality of life (QoL) assessment. In total 66 eyes of 62 patients were irradiated with a median dose of 30.6 Gy. The median follow-up was 43.5 months. The predominant histological subtype were MALT lymphomas. No local failure occurred in this cohort. Of nine outfield relapses, six solely occurred in the contralateral eye. The 5- and 10- years distant progression free survival rates (PFS) were 81.4% and 63.5%. The 5- and 10-years overall survival rates were 85.1% and 71.9% without any tumor related death. Of the acute toxicities none was higher than CTCAE grade 1. The predominant late toxicities were dry eyes (21.2%) of CTCAE Grade <2 and radiation induced cataracts (19.7%). During long-term follow up the average visual acuity did not deteriorate. The global QoL was worst before treatment and improved significantly after 24 months (p = 0.007). External beam radiotherapy of "orbital-type" lymphomas with photons is an effective and gentle treatment option with excellent local control rates. From the high control rates the trend to use slightly lower total doses of 24-27 Gy with conventional fractionation is supported. As non-coplanar radiotherapy techniques improved and total doses can slightly be reduced, the current status of radiotherapy as first line therapy is provided.

PROGNOSTIC VALUE OF POST-INDUCTION CHEMOTHERAPY VOLUMETRIC PET/CT PARAMETERS FOR STAGE IIIA/B NON-SMALL CELL LUNG CANCER PATIENTS RECEIVING DEFINITIVE CHEMORADIOTHERAPY.

Purpose/Objective(s): The aim of this follow-up analysis of the ESPATUE phase-3 trial was to explore the prognostic value of post-induction chemotherapy PET metrics in patients with stage III non-small cell lung cancer (NSCLC) who were assigned to receive definitive chemoradiotherapy. Materials/Methods: All eligible patients stage IIIA (cN2) and stage IIIB of the trial received induction chemotherapy consisting of 3 cycles of cisplatin/paclitaxel and chemoradiotherapy up to 45 Gy/1.5 Gy per fraction twice-a-day, followed by a radiation-boost with 2 Gy once per day with concurrent cisplatin/vinorelbine. The protocol definition prescribed a total dose of 65-71 Gy. 18F-FDG-PET/CT (PETpre) was performed at study entry and before concurrent chemoradiotherapy (interim-PET; PETpost). Interim PETpost metrics and known prognostic clinical parameters were correlated in uni- and multivariable survival analyses. Leave-one-out cross-validation was used to show internal validity. Results: Ninety-two patients who underwent 18F-FDG-PET/CT after induction chemotherapy were enrolled. Median MTVpost value was 5.9 ml. Altogether 85 patients completed the whole chemoradiation with the planned total dose of 60-71 Gy. In univariable proportional hazard analysis, each of the parameters MTVpost, SUVmax(post) and TLGmax(post) was associated with overall survival (P < 0.05). Multivariable survival analysis, including clinical and post-induction PET parameters, found TLGmax(post) (hazard ratio: 1.032 (95%-CI: 1.013-1.052) per 100 ml increase) and total radiation dose (hazard ratio: 0.930 (0.902-0.959) per Gray increase) significantly related with overall survival in the whole group of patients, and also in patients receiving a total dose ≥ 60 Gy. The best leave-one-out cross-validated 2 parameter classifier contained TLGmax(post) and total radiation dose. TLGmax(post) was associated with time to distant metastases (P = 0.0018), and SUVmax(post) with time to loco-regional relapse (P = 0.039) in multivariable analysis of patients receiving a total dose ≥ 60 Gy. Conclusion: Post-induction chemotherapy PET parameters demonstrated prognostic significance. Therefore, an interim 18F-FDG-PET/CT is a promising diagnostic modality for guiding individualized treatment intensification.

New model for long-term investigations of cutaneous microcirculatory and inflammatory changes following irradiation.

Radiotherapy is used for curative and palliative treatment. However, its negative effect on normal tissue is a limiting factor for the deliverable dose. Microcirculatory breakdown and prolonged inflammation in particular are major features of late side effects. The purpose of this study was to develop a reliable animal model that will allow a long-term in vivo analysis of microcirculation and inflammation following irradiation. A single dose of 90 Gy was delivered to the ears of hairless mice (n = 15). Intravital fluorescent microscopy was used to assess microcirculatory parameters and leukocyte behaviour. Values for the identical (control) areas were obtained before as well as during the following days, weeks and months following irradiation. The arteriolar and venular diameter increased up to Day 14, decreased during the following months, and increased again after one year. The red blood cell velocity increased up to 145% on Day 3, decreased on Day 7 to 115%, and stayed above baseline value the whole year. The integrity loss of the endothelium increased up to Day 7 and continued up to Day 75 after radiation. After one year, the oedema was at the baseline level. Leukocytes showed their maximal activity at one year after trauma. An increase was measured up to Day 25; the lowest values were measured at Day 40 post-irradiation, followed by a repeated increase. The present model allows a certain visualization of microcirculatory disturbances and inflammation over a period of months. This permits the possibility of long-term investigations of the underlying pathophysiology following irradiation, including possible drug interactions.

Hyperfractionated accelerated radiation therapy (HART) of 70.6 Gy with concurrent 5-FU/Mitomycin C is superior to HART of 77.6 Gy alone in locally advanced head and neck cancer: long-term results of the ARO 95-06 randomized phase III trial.

PURPOSE: To report the long-term results of the ARO 95-06 randomized trial comparing hyperfractionated accelerated chemoradiation with mitomycin C/5-fluorouracil (C-HART) with hyperfractionated accelerated radiation therapy (HART) alone in locally advanced head and neck cancer. PATIENTS AND METHODS: The primary endpoint was locoregional control (LRC). Three hundred eighty-four patients with stage III (6%) and IV (94%) oropharyngeal (59.4%), hypopharyngeal (32.3%), and oral cavity (8.3%) cancer were randomly assigned to 30 Gy/2 Gy daily followed by twice-daily 1.4 Gy to a total of 70.6 Gy concurrently with mitomycin C/5-FU (C-HART) or 16 Gy/2 Gy daily followed by twice-daily 1.4 Gy to a total dose of 77.6 Gy alone (HART). Statistical analyses were done with the log-rank test and univariate and multivariate Cox regression analyses. RESULTS: The median follow-up time was 8.7 years (95% confidence interval [CI]: 7.8-9.7 years). At 10 years, the LRC rates were 38.0% (C-HART) versus 26.0% (HART, P=.002). The cancer-specific survival and overall survival rates were 39% and 10% (C-HART) versus 30.0% and 9% (HART, P=.042 and P=.049), respectively. According to multivariate Cox regression analysis, the combined treatment was associated with improved LRC (hazard ratio [HR]: 0.6 [95% CI: 0.5-0.8; P=.002]). The association between combined treatment arm and increased LRC appeared to be limited to oropharyngeal cancer (P=.003) as compared with hypopharyngeal or oral cavity cancer (P=.264). CONCLUSIONS: C-HART remains superior to HART in terms of LRC. However, this effect may be limited to oropharyngeal cancer patients.

10-year long-term survival (LTS) of induction chemotherapy with three cycles cisplatin/paclitaxel followed by concurrent chemoradiation cisplatin/etoposide/45 Gy (1.5 Gy bid) plus surgery in locally advanced non-small-cell lung cancer (NSCLC)-a multicenter phase-II trial (CISTAXOL).

BACKGROUND: Induction chemoradiotherapy plus surgery remains an option to study in IIIA(N2) and selected IIIB NSCLC. Here we report ten-year long-term survival of a prospective multicenter German-French phase-II trial with trimodality. PATIENTS AND METHODS: Mediastinoscopically proven IIIA(N2)/selected IIIB NSCLC received three cycles cisplatin (50 mg/m(2) day 1+8) and paclitaxel (175 mg/m(2)d1) qd 22. Concurrent CTx/RTx followed: 45 Gy (1.5 Gy bid) with cisplatin 50 mg/m(2) day 2+9 and etoposide 100 mg/m(2) d 4-6. Surgery was planned three to five weeks after RTx. If evaluated inoperable/irresectable at the end of RTx, definitive RTx-boost (20 Gy; 2 Gy qd) followed. Here we report 10-year-LTS for this cohort. RESULTS: All 64 patients were accrued 3/99 to 2/02. Patients characteristics: IIIA(N2)/IIIB 25/39; m/f 48/16; adeno/squamous/large-cell/adenosquamous/NOS 15/26/18/3/2; age: median 52.5 (range 33-69). 36 operated: R0 32/36 (89%); pCR 16/36 (44%). 10-year-LTS%; all 26.0; IIIA(N2) 37.1; IIIB 17.9; relevant prognostic factors (exploratory): pretreatment - histopathology (squamous/adeno) - age (<50/≥50) - Charlson-CI: 1/>1 - BMI (≥25/<25) - pack years smoking (≥10/<10); treatment-dependent - R0/no-R0. CONCLUSIONS: This regimen achieves substantial LTS. Interestingly, adenocarcinomas, older patients, unfavorable comorbidity scores, higher BMI and light smokers demonstrate poor long-term outcome even with aggressive trimodality. This dataset defines the rationale for our ongoing randomized trial with surgery after induction therapy in IIIA(N2)/selected IIIB (ESPATÜ).

Prognostic impact of lymph node involvement in pulmonary metastases from colorectal cancer.

OBJECTIVE: The purpose of this study was to identify the prognostic impact of unexpected lymph node metastases in patients undergoing resection of pulmonary metastases from colorectal cancer and specify the influence of pulmonary and mediastinal nodal involvement according to the modified Narukes lymph node mapping [Mountain CF, Dresler CM. Regional lymph node classification for lung cancer. Chest 1997;111(6):1718-23.]. METHODS: From January 1993 to December 2003, 175 patients were diagnosed and resected for pulmonary metastases of colorectal cancer. Follow up informations were collected for 169 patients and an analysis of prognostic factors was performed. Ninety-six men (56.8%) and 73 women (43.2%) with a median age of 62 (range 34-81) were identified, 28 (16.7%) patients were found to have lymph node metastases, five of them were identified during a recurrent procedure. Probability of survival was calculated according to the method of Kaplan-Meier. The prognostic influence of lymph node metastases on survival was analyzed with the log-rank test. RESULTS: Median survival was 47.2 months after first metastasectomy. Ten patients with intrapulmonary nodal involvement had a median survival of 86 months whereas 12 patients with hilar and six patients with mediastinal lymph node metastases had a median survival of 24.5 and 34.7 months. The survival difference between pulmonary and hilar/mediastinal metastases was statistically significant (p=0.008/p=0.07). Five year survival with pulmonary, hilar, and mediastinal metastases was 78.5, 0, and 0%, respectively. Perioperative mortality was 0%. CONCLUSIONS: Resection of pulmonary metastases secondary to colorectal cancer is safe and indicated in highly selected patients. Because tumor involvement of lymph nodes has a strong impact on survival; depending on their location, at least a lymph node sampling should always be performed. Adjuvant chemotherapy in case of proven lymph node metastases might be a good option to improve prognosis.

Correlation of PET/CT findings and histopathology after neoadjuvant therapy in non-small cell lung cancer.

OBJECTIVES: Prediction of histopathological response with PET/CT scans after neoadjuvant chemoradiotherapy is limited by confounding factors which have been evaluated in this analysis. METHODS: (18)F-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT findings [standard uptake value (SUV), residual tumor volume] were correlated with histopathological parameters of the resection specimens (tumor cell density, necrosis, scar, macrophage infiltration) in patients with locally advanced non-small cell lung cancer (stage IIIA/IIIB) after neoadjuvant induction chemotherapy (platinum-based doublet) and concurrent chemoradiotherapy (cisplatin/vinorelbine/45 Gy). RESULTS: Sixty patients [40 male/20 female, median age 56 years (34-78)] completed induction therapy, 46 patients (stage IIIA/IIIB: 16/30; squamous cell carcinoma 41%, adenocarcinoma 48%, large cell carcinoma 11%) were resected. Pathologic complete response of the primary tumor was observed in 19 patients (41%) with a broad range of SUV(mean) (0.4-9.8, mean 3.0) after neoadjuvant therapy. A high rate of histopathological complete remissions (44%) was observed in tumors with a postinduction SUV >2.5 and volumes larger than the median (7.9 cm(3)) before resection. SUV(mean) was positively correlated with the macrophage score (r = 0.39, p = 0.007) and tumor cell density (r = 0.32, p = 0.03). CONCLUSIONS: These observations suggest that postinduction FDG uptake should be interpreted with caution in larger residual tumor volumes, since high SUV levels may be due to macrophage infiltration and not viable tumor tissue.