Combined tumor plus nontumor interim FDG-PET parameters are prognostic for response to chemoradiation in squamous cell esophageal cancer

We have investigated the prognostic value of two novel interim ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) parameters in patients undergoing chemoradiation (CRT) for esophageal squamous cell carcinoma (ESCC): one tumor parameter (maximal standardized uptake ratio rSUR) and one normal tissue parameter (change of FDG uptake within irradiated nontumor-affected esophagus ∆SUV_NTO). PET data of 134 European and Chinese patients were analyzed. Parameter establishment was based on 36 patients undergoing preoperative CRT plus surgery, validation was performed in 98 patients receiving definitive CRT. Patients received PET imaging prior and during fourth week of CRT. Clinical parameters, baseline PET parameters, and interim PET parameters (rSUR and ∆SUV_NTO) were analyzed and compared to event-free survival (EFS), overall survival (OS), loco-regional control (LRC) and freedom from distant metastases (FFDM). Combining rSUR and ∆SUV_NTO revealed a strong prognostic impact on EFS, OS, LRC and FFDM in patients undergoing preoperative CRT. In the definitive CRT cohort, univariate analysis with respect to EFS revealed several staging plus both previously established interim PET parameters as significant prognostic factors. Multivariate analyses revealed only rSUR and ∆SUV_NTO as independent prognostic factors (p = 0.003, p = 0.008). Combination of these parameters with the cutoff established in preoperative CRT revealed excellent discrimination of patients with a long or short EFS (73% vs. 17% at 2 years, respectively) and significantly discriminated all other endpoints (OS, p < 0.001; LRC, p < 0.001; FFDM, p = 0.02), even in subgroups. Combined use of interim FDG-PET derived parameters ∆SUV_NTO and rSUR seems to have predictive potential, allowing to select responders for definitive CRT and omission of surgery.     

MET Y1253D-activating point mutation and development of distant metastasis in advanced head and neck cancers

We investigated if the MET-activating point mutation Y1253D influences clinical outcomes in patients with advanced squamous cell carcinoma of the head and neck (HNSCC). The study population consisted of 152 HNSCC patients treated by hyperfractionated radiotherapy alone or concomitant with chemotherapy between September 1994 and July 2000. Tumors were screened for the presence of the MET-activating point mutation Y1253D. Seventy-eight patients (51%) received radiotherapy alone, 74 patients (49%) underwent radiotherapy concomitant with chemotherapy. Median patient age was 54 years and median follow-up was 5.5 years. Distant metastasis-free survival, local relapse-free survival and overall survival were compared with MET Y1253D status. During follow-up, 29 (19%) patients developed distant metastasis. MET Y1253D was detected in tumors of 21 out of 152 patients (14%). Distant metastasis-free survival (P = 0.008) was associated with MET Y1253D. In a multivariate Cox regression model, adjusted for T-category, only presence of MET Y1253D was associated with decreased distant metastasis-free survival: hazard ratio = 2.5 (95% confidence interval: 1.1, 5.8). The observed association between MET Y1253D-activating point mutation and decreased distant metastasis-free survival in advanced HNSCC suggests that MET may be a potential target for specific treatment interventions.     

Chemokine receptor CCR6 expression level and aggressiveness of prostate cancer

Purpose  CCR6 is expressed in various tumors and has been implicated in the process of tumor progression and metastasis. Its chemokine ligand, CCL20, is present in different tissues including lymph nodes, but also the normal prostate. This study was performed to investigate a potential relationship between CCR6 and CCL20 expression and features of human prostate cancer (PCA) at time of primary treatment. Methods  Immunohistochemistry was used to detect CCR6 and CCL20 expression in archival tissue blocks of 80 PCA cases of various tumor grades and stages. Evaluation was semiquantitatively by visual scoring and quantitatively by digital image analysis (DIA). CCR6 and CCL20 expression was compared with Gleason score, stage, perineural invasion, nodal metastasis, age, and preoperative serum prostate-specific antigen (PSA) level by univariate and multivariate analyses. Results  Staining intensity of CCR6 in tumor cells varied considerably, with it being: weak in 21 tumors (26.2%), intermediate in 44 (55.0%), and strong in 15 (18.8%), with 3.6-log differences in DIA measurements. CCL20 expression was absent in eight tumors (10.0%), weak in 41 (51.2%), intermediate in 23 (28.8%), and strong in eight (10.0%). CCR6 and CCL20 expression did not correlate. CCR6 expression was associated with T-category (P < 0.0005), Gleason score (P = 0.003), and lymph node metastasis (P = 0.002). Conclusions  Expression levels of CCR6 in PCA were associated with clinical and pathologic features of more advanced and aggressive prostate cancer. Thus, CCR6 may directly or indirectly be involved in tumor progression and should be evaluated as novel candidate target molecule for specific treatment interventions.     

Induction chemotherapy for unresectable urothelial carcinoma of the bladder

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? In resectable muscle‐invasive bladder cancer neoadjuvant chemotherapy followed by radical cystectomy confers to a significant 5% overall survival benefit. Less is known about induction chemotherapy followed by radical cystectomy in initially unresectable patients. Our retrospective analysis of a selected patient cohort suggests that patients with initially unresectable bladder cancer may benefit from this combined treatment approach.

OBJECTIVE

? To analyse the outcome in selected patients with initially unresectable or minimally metastatic muscle‐invasive urothelial bladder cancer who underwent induction chemotherapy (IC) followed by radical cystectomy (RC).

PATIENTS AND METHODS

? Thirty patients with initially unresectable, locally advanced or minimally metastatic bladder cancer underwent platinum‐based IC followed by RC with curative intent at our institution from 2000 to 2007. ? They received a median of four cycles (range 2–6 cycles) of cisplatin and gemcitabine (n= 19), carboplatin and gemcitabine (n= 9) or other platinum combinations (n= 2). ? We retrospectively analysed all 30 patients for complete pathological remission (pT0), disease free survival (DFS) and overall survival (OS). Chi‐square tests, Kaplan–Meier analyses, and Cox univariate modelling were used.

RESULTS

? Before IC, 30 patients were deemed unresectable because of locally advanced tumour classification (cT4, 18/30) and/or clinically suspected lymph node (LN) metastasis (21/30) or suspected distant metastasis (3/30). ? At re‐staging after IC there was a complete regression of all enlarged LN in 16/21 patients, a partial LN response in one patient or stable LN size in the remaining four patients. ? After RC, 9/30 (30%) of patients had attained pT0. ? The median follow‐up was 28 months (range 4–97 months). The 5‐year DFS and OS rates were 42% and 46%, respectively, for all patients. ? In the pT0 patients, the DFS (83%) and OS (71%) rates were significantly higher than in non‐pT0 patients.

CONCLUSION

? Patients undergoing IC followed by RC showed encouraging response and survival rates, suggesting that selected patients with initially unresectable bladder cancer benefit from this combined regimen.     

Locally dose-escalated radiotherapy may improve intracranial local control and overall survival among patients with glioblastoma

Background

The dismal overall survival (OS) prognosis of glioblastoma, even after trimodal therapy, can be attributed mainly to the frequent incidence of intracranial relapse (ICR), which tends to present as an in-field recurrence after a radiation dose of 60 Gray (Gy). In this study, molecular marker-based prognostic indices were used to compare the outcomes of radiation with a standard dose versus a moderate dose escalation.

Methods

This retrospective analysis included 156 patients treated between 2009 and 2016. All patients were medically fit for postoperative chemoradiotherapy. In the dose-escalation cohort a simultaneous integrated boost of up to 66?Gy (66?Gy RT) within small high-risk volumes was applied. All other patients received daily radiation to a total dose of 60?Gy or twice daily to a total dose of 59.2?Gy (60?Gy RT).

Results

A total of 133 patients received standard 60?Gy RT, while 23 received 66?Gy RT. Patients in the 66?Gy RT group were younger (p?<? 0.001), whereas concomitant temozolomide use was more frequent in the 60?Gy RT group (p?<? 0.001). Other intergroup differences in known prognostic factors were not observed. Notably, the median time to ICR was significantly prolonged in the 66?Gy RT arm versus the 60?Gy RT arm (12.2 versus 7.6?months, p?=?0.011), and this translated to an improved OS (18.8 versus 15.3?months, p?=?0.012). A multivariate analysis revealed a strong association of 66?Gy RT with a prolonged time to ICR (hazard ratio?=?0.498, p?=?0.01) and OS (hazard ratio?=?0.451, p?=?0.01). These differences remained significant after implementing molecular marker-based prognostic scores (ICR p?=?0.008, OS p?=?0.007) and propensity-scored matched pairing (ICR p?=?0.099, OS p?=?0.023).

Conclusion

Radiation dose escalation was found to correlate with an improved time to ICR and OS in this cohort of glioblastoma patients. However, further prospective validation of these results is warranted.

     

Use of androgen deprivation and salvage radiation therapy for patients with prostate cancer and biochemical recurrence after prostatectomy

Aim

Overview on the use of androgen deprivation therapy (ADT) added to salvage radiation therapy (SRT) for prostate cancer patients with biochemical recurrence after prostatectomy.

Methods

The German Society of Radiation Oncology (DEGRO) expert panel summarized available evidence published between January 2009 and May 2017, and assessed the validity of the information on outcome parameters including overall survival (OS) and treatment-related toxicity.

Results

Two randomized controlled trials and nine relevant retrospective analyses were identified. The RTOG 9601 trial showed an OS improvement for the combination of 2 years of bicalutamide and SRT compared to SRT alone after a median follow-up of 13 years. This improvement appeared to be restricted to those patients with a prostate specific antigen (PSA) level before SRT of ≥0.7?ng/mL. The GETUG AFU-16 trial showed that after a median follow-up of 5 years, the addition of 6 months of goserelin to SRT improved progression-free survival (PFS; based on biochemical recurrence) as compared to SRT alone. ADT in both trials was not associated with increased major late toxicities. Results of retrospective series were inconsistent with a suggestion that the addition of ADT improved biochemical PFS especially in patients with high-risk factors such as Gleason Score ≥8 and in the group with initially negative surgical margins.

Conclusions

ADT combined with SRT appears to improve OS in patients with a PSA level before SRT of ≥0.7?ng/mL. In patients without persistent PSA after prostatectomy and PSA levels of <0.7?ng/mL, ADT should not routinely be used, but may be considered in patients with additional risk factors such as Gleason Score ≥8 and negative surgical margins.