Regional nodal relapse in surgically staged Merkel cell carcinoma

Purpose

The nodal relapse pattern of surgically staged Merkel cell carcinoma (MCC) with/without elective nodal radiotherapy (RT) was studied in a single institution.

Method

A total of 51 patients with MCC, 33?% UICC stage I, 14?% II, 53?% III (4 lymph node metastases of unknown primary) were eligible. All patients had surgical staging: 23 patients sentinel node biopsy (SNB), 22 patients SNB followed by lymphadenectomy (LAD) and 6 patients LAD. In all, 94?% of the primary tumors (PT) were completely resected; 57?% of patients received RT, 51?% of known PT sites, 33?% (8/24 patients) regional RT to snN0 nodes and 68?% (17/27 patients) to pN+ nodes, mean reference dose 51.5 and 50 Gy, respectively. Mean follow-up was 6 years (range 2–14 years).

Results

A total of 22?% (11/51) patients developed regional relapses (RR); the 5-year RR rate was 27?%. In snN0 sites (stage I/II), relapse occurred in 5 of 14 nonirradiated vs. none of 8 irradiated sites (p?=?0.054), resulting in a 5-year RR rate of 33?% versus 0?% (p?=?0.16). The crude RR rate was lower in stage I (12?%, 2/17 patients) than for stage II (43?%, 3/7 patients). In stage III (pN+), RR appeared to be less frequent in irradiated sites (18?%, 3/14 patients) compared with nonirradiated sites (33?%, 3/10 patients, p?=?0.45) with 5-year RR rates of 23?% vs. 34?%, respectively.

Discussion

Our data suggest that adjuvant nodal RT plays a major role even if the sentinel nodes were negative.

Conclusion

Adjuvant RT of the lymph nodes in patients with stage IIa tumors and RT after LAD in stage III tumors is proposed and should be evaluated prospectively.

     

Prognostic importance of tobacco use in men receiving definitive prostate brachytherapy

PurposeSeveral prominent publications have identified an overall association between tobacco use and an increased risk of disease recurrence and disease-specific mortality in prostate cancer patients. The authors explored whether tobacco use adversely impacts treatment outcomes in men treated with permanent interstitial brachytherapy.Methods and MaterialsFrom April 1995 to August 2008, 2057 patients underwent brachytherapy by a single brachytherapist. Median follow-up was 7.5 years. The role of tobacco use as a prognostic factor for biochemical progression-free survival, cause-specific survival, and overall survival was investigated. Differences in survival between smokers and nonsmokers were compared using Kaplan–Meier curves and log-rank tests.ResultsCurrent smokers presented with a lower body mass index (p < 0.001), smaller prostate size (p = 0.003), younger age (p < 0.001), higher prostate-specific antigen level (p = 0.002), a trend toward higher percentage biopsy core involvement (p = 0.08), higher incidence of perineural invasion (p = 0.015), and higher risk disease (p < 0.001) than former or nonsmokers. There was no difference in biochemical progression-free survival (p = 0.30) or cause-specific survival (p = 0.72) at 10 years for smokers compared with nonsmokers. On univariate and multivariate analysis, tobacco use was an adverse risk factor for overall survival (p < 0.001). There was no association between smoking and any prostate cancer-specific outcome.ConclusionsSmokers treated with brachytherapy have excellent outcomes and are at no higher risk of treatment failure than men who are nonsmokers.     

Ultra hypofractionated extended nodal irradiation using volumetric modulated arc therapy for oligorecurrent pelvic nodal prostate cancer

Prostate cancer (PCa) may recur after primary treatment but no standard of care exists for patients with pelvic nodal relapse. Based on obervational data, Extended Nodal Irradiation (ENI) might be associated with fewer treatment failures than Stereotactic Ablative Radiotherapy (SABR) to the involved node(s) alone. Ultra hypofractionated ENI is yet to be evaluated in this setting, but it could provide a therapeutic advantage if PCa has a low α/β ratio in addition to patient convenience/resource benefits. This volumetric modulated arc therapy (VMAT) planning study developed a class solution for 5-fraction Extended Nodal Irradiation (ENI) plus a simultaneous integrated boost (SIB) to involved node(s). Ten patients with oligorecurrent nodal disease after radical prostatectomy/post-operative prostate bed radiotherapy were selected. Three plans were produced for each dataset to deliver 25 Gy in 5 fractions ENI plus SIBs of 40, 35 and 30 Gy. The biologically effective dose (BED) formula was used to determine the remaining dose in 5 fractions that could be delivered to re-irradiated segments of organs at risk (OARs). Tumour control probability (TCP) and normal tissue complication probability (NTCP) were calculated using the LQ-Poisson Marsden and Lyman-Kutcher-Burman models respectively. Six patients had an OAR positioned within planning target volume node (PTVn), which resulted in reduced target coverage to PTV node in six, five and four instances for 40, 35 and 30 Gy SIB plans respectively. In these instances, only 30 Gy SIB plans had a median PTV coverage >90% (inter-quartile range 90-95). No OAR constraint was exceeded for 30 Gy SIB plans, including where segments of OARs were re-irradiated. Gross tumour volume node (GTVn) median TCP was 95.7% (94.4-96), 90.7% (87.1-91.2) and 78.6% (75.8-81.1) for 40, 35 and 30 Gy SIB plans respectively, where an α/β ratio of 1.5 was assumed. SacralPlex median NTCP was 43.2% (0.7-61.2), 12.1% (0.6-29.7) and 2.5% (0.5-5.1) for 40, 35 and 30 Gy SIB plans respectively. NTCP for Bowel_Small was <0.3% and zero for other OARs for all three plan types. Ultra hypofractionated ENI planning for pelvic nodal relapsed PCa appears feasible with encouraging estimates of nodal TCP and low estimates of NTCP, especially where a low α/β ratio is assumed and a 30 Gy SIB is delivered. This solution should be further evaluated within a clinical trial and compared against SABR to involved node(s) alone.     

Role of 18F-choline PET/CT in suspicion of relapse following definitive radiotherapy for prostate cancer

Purpose

The aims of the study were (a) to evaluate the diagnostic role, by means of positive detection rate (PDR), of ¹⁸F-choline (CH) positron emission tomography (PET)/CT in patients with prostate cancer treated with radiotherapy, with curative intent, and suspicion of relapse during follow-up, (b) to correlate the PDR with trigger prostate-specific antigen (PSA), (c) to investigate the possible influence of androgen deprivation therapy (ADT) at the time of scan on PDR and (d) to assess distribution of metastatic spread.

Methods

¹⁸F-CH PET/CT exams from 46 consecutive patients (mean age 71.3 years, range 51–84 years) with prostate cancer (mean Gleason score 6.4, range 5–8) previously treated by definitive radiotherapy and with suspicion of relapse with negative or inconclusive conventional imaging were retrospectively evaluated. Of the 46 patients, 12 were treated with brachytherapy and 34 with external beam radiation therapy. Twenty-three patients were under ADT at the time of the examination. Trigger PSA was measured within 1 month before the exam (mean value 6.5 ng/ml, range 1.1–49.4 ng/ml). Patients were subdivided into four groups according to their PSA level: 1.0?<?PSA?≤?2.0 ng/ml (11 patients), 2.0?<?PSA?≤?4.0 ng/ml (16 patients), 4.0?<?PSA?≤?6.0 ng/ml (9 patients) and PSA?>?6.0 ng/ml (10 patients). Correlation between ADT and PDR was investigated as well as between PSA and distribution of metastatic spread.

Results

The overall PDR of ¹⁸F-CH PET/CT was 80.4 % (37/46 patients), increasing with the increase of trigger PSA. PDR of ¹⁸F-CH PET/CT is not influenced by ADT (p?=?0.710) even if PET performed under ADT demonstrated an overall higher PDR (82.6 %). The majority of the patients (59 %, 22/37 patients) showed local relapse only, confined to the prostatic bed; 22 % of the PET/CT-positive patients (8/37 patients) showed distant relapse only (bone localizations in all of them), while the remaining 19 % (7/37 patients) showed both local and distant (lymph node and bone) spread.

Conclusion

¹⁸F-CH PET/CT showed a high overall detection rate (80 %), proportional to the trigger PSA (both for local and distant relapse) not influenced by ADT. ¹⁸F-CH PET/CT is proposed as a first-line imaging procedure in restaging prostate cancer patients primarily treated with radiotherapy.     

Mammographic findings after breast cancer treatment with local excision and definitive irradiation

Following local excision and definitive irradiation of 163 breast cancers in 160 women, alterations in mammographic patterns were observed for up to 7 years. Skin thickening was observed in 96% of mammograms obtained within 1 year of completing therapy and was most pronounced in women treated with iridium implant, chemotherapy, or axillary dissection. In 76% of mammograms, alterations in the parenchymal pattern, including coarsening of stroma and increased breast density, were seen at 1 year. Neither skin nor parenchymal changes progressed after 1 year. Within 3 years of treatment the parenchymal density, which usually regressed, did not change in all patients. At 3 years skin thickness and the parenchymal pattern had returned to normal in less than 50% of the breasts of these women. Scars developed in approximately one-quarter of women. They were present on the initial post-treatment mammogram and remained unchanged on serial studies. Coarse, benign calcifications also developed in the breasts of about one-quarter of women. Microcalcifications developed in 11 breasts; biopsy specimens of six were benign. Benign microcalcifications may be related to therapy.     

Predictive factors for radiation pneumonitis in oesophageal cancer patients treated with chemoradiotherapy without prophylactic nodal irradiation

Objective

The objective of this study was to identify clinical and dosimetric factors for the development of radiation pneumonitis (RP) among patients with oesophageal cancer treated with three-dimensional radiotherapy without prophylactic nodal irradiation.

Methods

125 patients with oesophageal cancer had undergone dose–volume histogram (DVH) metrics and received chemoradiotherapy (CRT). Several clinical and dosimetric factors with regard to the lung were evaluated as predictive factors for the development of symptomatic RP.

Results

26 patients (20.8%) developed symptomatic RP classified as greater than or equal to Grade 2. By univariate analysis, body weight loss, tumour length, Stage IV, response to treatment and all DVH parameters proved to be significant factors for the development of RP (p<0.05). By multivariate analysis, Stage IV and all dosimetric factors were independent predictive factors for the development of symptomatic RP (p<0.05). Recursive partitioning analysis indicated that V10 values of 24.8% or more and Stage IV were associated with higher development of RP (odds ratio 6.53).

Conclusions

Our study demonstrated that severe RP was also developed in patients treated with the minimal radiation field. Stage IV and the dosimetric factors were identified as independent predictive factors for symptomatic RP in oesophageal cancer patients treated with CRT without prophylactic nodal irradiation.Definitive chemoradiotherapy (CRT) has been established as a curative option for patients with carcinoma of the oesophagus, and its clinical efficacy has expanded [1-4]. Because thoracic irradiation can cause late development of adverse events that involve the heart, lung and oesophagus, including death, radiation therapy management has become an important clinical issue, especially for patients with prolonged survival and follow-up [5-9]. Efforts to reduce adverse events have become increasingly important.Radiation pneumonitis (RP) is a major adverse event after thoracic irradiation, which occasionally results in death. In several studies, predictive factors for RP, including clinical factors and dosimetric parameters, have been reported for patients with lung cancer receiving definitive radiotherapy (RT) [10-14]. However, in oesophageal cancer, few reports are available on predictive factors for RP [15,16]. To our knowledge, the predictive factors for the development of RP have not been evaluated in detail for oesophageal cancer patients treated with minimal radiation field.The objective of the present study was to determine the predictive values of clinical and dosimetric factors for the development of symptomatic RP in oesophageal cancer patients treated with three-dimensional (3D) RT without prophylactic nodal irradiation.     

食管癌调强放疗淋巴引流区预防照射的同期对照研究

目的：探讨应用调强技术进行食管癌根治性放疗患者淋巴引流区预防照射的价值,筛选出淋巴引流区预防照射的适合人群,以进一步提高局部控制,改善长期生存。方法：对根治性放疗的食管癌初治患者进行同期对照研究,完成治疗计划且资料完整可供分析者148例,74例接受选择性淋巴引流区预防照射（ENI）,74例接受累及野照射（IFI）。采用Kaplan-Meier法计算两组患者局部控制率和生存率并进行单因素和多因素预后分析。结果：ENI组与IFI组1、3、5年局部控制率分别为72.5%、52.8%、50.6%和58.4%、35.8%、21.9%（χ²=7.881,P<0.05）。ENI组与IFI组1、3、5年生存率分别为74.3%、44.2%、24.5%和68.9%、27.6%、15.9%（χ²=1.903,P<0.05）。多因素分析发现临床T分期、病变部位、照射方式是影响全组患者局部控制的独立性因素,T分期、N分期、钡餐造影长度和化疗是影响全组患者生存的独立性因素。结论：ENI组的局部控制率较IFI显著提高,早期和胸中段食管癌患者行ENI照射局部控制及生存均能获益。     

Prognostic factors for local recurrence in patients with limited surgery and irradiation of breast cancer

Between January 1975 and December 1984, 239 patients after breast conserving surgery were referred to the University Clinic for Radiotherapy and Radiobiology of Vienna. Of these patients 214 were available for analysis with regard to loco-regional control and cosmetic outcome. The breast received supervoltage irradiation from two tangential fields, in 82% with a tumor dose of 50 Gy and in 15% 50 to 60 Gy. In addition 70% of the patients received a boost dose with 7.5 to 15 MeV electrons to the tumor bed and the scar. The overall local failure rate was 10.2%. For patients with T1,2 and negative axillary nodes or less than four positive lymph nodes (N = 160) a recurrence rate of 7.1% was observed. Factors correlated to a higher local recurrence rate were in this retrospective study axillary status (greater than 3 positive lymph nodes), histopathologic grade (G III), absence of clear margin after surgery and absence of additional electron boost.     

Multivariate analysis of dissemination relapse of medulloblastoma and estimation of its time parameter for craniospinal irradiation

PURPOSE: To examine in retrospect prognostic factors influencing meningeal dissemination relapse of medulloblastoma (MB) and to estimate time parameter gamma/alpha of the biologically effective dose for fractionated craniospinal irradiation (CSI). MATERIALS AND METHODS: Fifty-eight patients with MB who had been treated at our six hospitals from 1980 to 1990, were analyzed by the proportional hazards model consisting of radiation factors of both CSI and local irradiation (LI), sequential CSI time-lag, and eight non-radiation factors (gender, age, performance status, T-stage, dissemination score, extent of resection, and use of chemotherapy and immunotherapy). The gamma/alpha for CSI was estimated by the profile likelihood method using the maximum value of conditionally calculated time-incorporated biologically effective dose, tBEDmax, of the field treated with the least dose. RESULTS: Dissemination relapse was seen in 23 (40%) patients. Nineteen disseminations occurred within four years, and the cumulative dissemination-free rate was 64% at five years. The site of initial dissemination relapse was both cranial and spinal in 13 patients (57%). Dissemination relapse was accompanied with local failure in 43% (10/23) of patients, and four of them were seen later than four years. In the multivariate analysis, significant prognostic factors were dissemination score (p=0.0008) and total dose of CSI (p=0.018). The estimate of gamma/alpha for CSI was about 0.2 Gy/day in BED units. In another multivariate analysis including the best-fitted tBEDmax, significant prognostic factors were dissemination score and the tBEDmax of both CSI (p=0.021) and LI (p=0.024). CONCLUSION: This analysis indicated that the dissemination score, total dose of CSI, and tBEDmax of both CSI and LI were significantly prognostic for dissemination relapse of MB. The estimate of gamma/alpha for CSI was smaller than that derived from our previous analysis for LI. However, in order to estimate the time factor for CSI more precisely, a larger group of patients treated with concurrent CSI is needed.     

Prognostic impact of identifying etiology of prosthetic valve dysfunction with CT

BackgroundIn patients with prosthetic heart valves (PHV), there are distinct treatment implications based on prosthetic valve dysfunction (PVD) etiology. We investigated whether evaluation for PVD etiology on computed tomography (CT) has prognostic value for adverse clinical outcomes.MethodsConsecutive patients with suspected PVD that had a clinically indicated contrast chest CT and echocardiogram done within 1 year of each other were identified retrospectively from the Prosthetic Heart Valve CT Registry at the University of Minnesota. CTs and echocardiograms were assessed for potential PVD etiologies of pannus, structural valve degeneration (SVD) and thrombus, as per standard guidelines. Kaplan-Meier and Cox regression analyses were performed to assess association with a composite outcome of reoperation and all-cause mortality.Results132 patients (51.5% male, mean age 62.1 ?± ?19.3 years) with suspected PVD were included. There were 97 tissue valves, 31 mechanical valves and 4 transcatheter valves. The location of the valve was as follows: 72 aortic, 45 mitral, 8 tricuspid, and 7 pulmonic. A PVD etiology was diagnosed on CT in 80 (60.6%) patients, and on echocardiography in 45 (34.1%) patients, largely driven by a diagnosis of SVD on both modalities. Significant univariate predictors of the composite outcome included CT diagnosis of SVD (P ?< ?0.001), echocardiography diagnosis of SVD (P ?< ?0.001), degree of prosthetic stenosis (P ?< ?0.001) and degree of prosthetic regurgitation (P ?< ?0.001). On multivariable analyses adjusted for age, sex, left ventricular function, degree of prosthetic stenosis and degree of prosthetic regurgitation, CT diagnosis of SVD was significantly associated with the composite outcome (HR: 1.79, 1.09–2.95) whereas echocardiography diagnosis of SVD was not (HR: 1.56, 0.98–2.46).ConclusionIn patients with suspected PVD, CT assessment of SVD had prognostic significance for hard outcomes. CT should be considered in the diagnostic evaluation of patients with suspected PVD.