Jarad Martin

Late Relapses of Germ Cell Malignancies: Incidence, Management, and Prognosis

Late relapses of malignant germ cell tumors (MGCTs) are rare and occur, by definition, 2 years or later after successful treatment. They represent a major challenge of todays treatment of MGCTs. Because of the rarity and heterogeneity of late relapses, many aspects of their main characteristics remain obscure. We present relevant literature on relapsing MGCTs to highlight the following issues: incidence, impact of initial treatment on the subsequent risk of late relapse, treatment, and survival. In a pooled analysis, the incidence is 1.4% and 3.2% in seminoma and nonseminoma patients, respectively. The predominant site of relapse is the retroperitoneal space in both histologic types. The initial treatment appears to be important for the risk and localization of late relapses. The treatment of late relapses should be based on a representative presalvage biopsy and includes radical surgery and salvage chemotherapy in most cases. Five-year cancer-specific survival is above 50% in the recent large series and reaches 100% in case of single-site teratoma. Diagnosis and treatment of late-relapsing MGCT patients is challenging and should be performed in experienced centers only. Referral of late-relapsing patients to high-volume institutions ensures the best chances of cure and enables increasing understanding of tumor biology and the clinical course of these patients.

Evidence-based guidelines for following stage 1 seminoma

The authors developed evidence‐based guidelines for a follow‐up schedule after orchiectomy for stage 1 seminoma. Required investigations, frequency of assessment, overall duration of follow‐up, and management strategies were identified.

Promising results with chemoradiation in patients with sinonasal undifferentiated carcinoma.

Sinonasal undifferentiated carcinoma (SNUC) is an uncommon malignancy associated with poor prognosis. The optimal treatment approach for SNUC has not been established was performed.

Paranasal sinus tumors: Peter maccallum cancer institute experience

The purpose of this study was to evaluate the local control, pattern of recurrence, overall survival, and prognostic factors of patients with squamous cell carcinoma (SCC), adenocarcinoma, and undifferentiated carcinoma of the paranasal sinuses (PNS) and nasal cavity (NC) presenting to our center for curative treatment over a 10‐year period.

Image guided dose escalated prostate radiotherapy: still room to improve

BackgroundProstate radiotherapy (RT) dose escalation has been reported to result in improved biochemical control at the cost of greater late toxicity. We report on the application of 79.8 Gy in 42 fractions of prostate image guided RT (IGRT). The primary objective was to assess 5-year biochemical control and potential prognostic factors by the Phoenix definition. Secondary endpoints included acute and late toxicity by the Radiotherapy Oncology Group (RTOG) scoring scales.MethodsFrom October/2001 and June/2003, 259 men were treated with at least 2-years follow-up. 59 patients had low, 163 intermediate and 37 high risk disease. 43 had adjuvant hormonal therapy (HT), mostly for high- or multiple risk factor intermediate-risk disease (n = 25). They received either 3-dimensional conformal RT (3DCRT, n = 226) or intensity modulated RT (IMRT) including daily on-line IGRT with intraprostatic fiducial markers.ResultsMedian follow-up was 67.8 months (range 24.4-84.7). There was no severe (grade 3-4) acute toxicity, and grade 2 acute gastrointestinal (GI) toxicity was unusual (10.1%). The 5-year incidence of grade 2-3 late GI and genitourinary (GU) toxicity was 13.7% and 12.1%, with corresponding grade 3 figures of 3.5% and 2.0% respectively. HT had an association with an increased risk of grade 2-3 late GI toxicity (11% v 21%, p = 0.018). Using the Phoenix definition for biochemical failure, the 5 year-bNED is 88.4%, 76.5% and 77.9% for low, intermediate and high risk patients respectively. On univariate analysis, T-category and Gleason grade correlated with Phoenix bNED (p = 0.006 and 0.039 respectively). Hormonal therapy was not a significant prognostic factor on uni- or multi-variate analysis. Men with positive prostate biopsies following RT had a lower chance of bNED at 5 years (34.4% v 64.3%; p = 0.147).ConclusionIGRT to 79.8 Gy results in favourable rates of late toxicity compared with published non-IGRT treated cohorts. Future avenues of investigation for toxicity reduction include IMRT, margin reduction, and dose modulation targeted to sites of disease burden. Further work is required to maximize efficacy beyond that achieved through radiation dose escalation alone.

Randomized Trial of a Hypofractionated Radiation Regimen for the Treatment of Localized Prostate Cancer

Purpose Men with localized prostate cancer often are treated with external radiotherapy (RT) over 8 to 9 weeks. Hypofractionated RT is given over a shorter time with larger doses per treatment than standard RT. We hypothesized that hypofractionation versus conventional fractionation is similar in efficacy without increased toxicity. Patients and Methods We conducted a multicenter randomized noninferiority trial in intermediate-risk prostate cancer (T1 to 2a, Gleason score ≤ 6, and prostate-specific antigen [PSA] 10.1 to 20 ng/mL; T2b to 2c, Gleason ≤ 6, and PSA ≤ 20 ng/mL; or T1 to 2, Gleason = 7, and PSA ≤ 20 ng/mL). Patients were allocated to conventional RT of 78 Gy in 39 fractions over 8 weeks or to hypofractionated RT of 60 Gy in 20 fractions over 4 weeks. Androgen deprivation was not permitted with therapy. The primary outcome was biochemical-clinical failure (BCF) defined by any of the following: PSA failure (nadir + 2), hormonal intervention, clinical local or distant failure, or death as a result of prostate cancer. The noninferiority margin was 7.5% (hazard ratio, < 1.32). Results Median follow-up was 6.0 years. One hundred nine of 608 patients in the hypofractionated arm versus 117 of 598 in the standard arm experienced BCF. Most of the events were PSA failures. The 5-year BCF disease-free survival was 85% in both arms (hazard ratio [short v standard], 0.96; 90% CI, 0.77 to 1.2). Ten deaths as a result of prostate cancer occurred in the short arm and 12 in the standard arm. No significant differences were detected between arms for grade ≥ 3 late genitourinary and GI toxicity. Conclusion The hypofractionated RT regimen used in this trial was not inferior to conventional RT and was not associated with increased late toxicity. Hypofractionated RT is more convenient for patients and should be considered for intermediate-risk prostate cancer.

Radiotherapy for perineural invasion in cutaneous head and neck carcinomas: Toward a risk-adapted treatment approach†

We retrospectively reviewed outcomes in patients treated with radiotherapy (RT) for cutaneous head and neck carcinoma with perineural invasion (PNI), with the aim of developing risk‐adapted treatment guidelines.

Prostate contouring variation: can it be fixed?

PURPOSE To assess whether an education program on CT and MRI prostate anatomy would reduce inter- and intraobserver prostate contouring variation among experienced radiation oncologists. METHODS AND MATERIALS Three patient CT and MRI datasets were selected. Five radiation oncologists contoured the prostate for each patient on CT first, then MRI, and again between 2 and 4 weeks later. Three education sessions were then conducted. The same contouring process was then repeated with the same datasets and oncologists. The observer variation was assessed according to changes in the ratio of the encompassing volume to intersecting volume (volume ratio [VR]), across sets of target volumes. RESULTS For interobserver variation, there was a 15% reduction in mean VR with CT, from 2.74 to 2.33, and a 40% reduction in mean VR with MRI, from 2.38 to 1.41 after education. A similar trend was found for intraobserver variation, with a mean VR reduction for CT and MRI of 9% (from 1.51 to 1.38) and 16% (from 1.37 to 1.15), respectively. CONCLUSION A well-structured education program has reduced both inter- and intraobserver prostate contouring variations. The impact was greater on MRI than on CT. With the ongoing incorporation of new technologies into routine practice, education programs for target contouring should be incorporated as part of the continuing medical education of radiation oncologists.

Perineural Infiltration of Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma Without Clinical Features

PURPOSE To review the factors that influence outcome and patterns of relapse in patients with cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) with perineural infiltration (PNI) without clinical or radiologic features, treated with surgery and radiotherapy. METHODS AND MATERIALS Between 1991 and 2004, 222 patients with SCC or BCC with PNI on pathologic examination but without clinical or radiologic PNI features were identified. Charts were reviewed retrospectively and relevant data collected. All patients were treated with curative intent; all had radiotherapy, and most had surgery. The primary endpoint was 5-year relapse-free survival from the time of diagnosis. RESULTS Patients with SCC did significantly worse than those with BCC (5-year relapse-free survival, 78% vs. 91%; p < 0.01). Squamous cell carcinoma with PNI at recurrence did significantly worse than de novo in terms of 5-year local failure (40% vs. 19%; p < 0.01) and regional relapse (29% vs. 5%; p < 0.01). Depth of invasion was also a significant factor. Of the PNI-specific factors for SCC, focal PNI did significantly better than more-extensive PNI, but involved nerve diameter or presence of PNI at the periphery of the tumor were not significant factors. CONCLUSIONS Radiotherapy in conjunction with surgery offers an acceptable outcome for cutaneous SCC and BCC with PNI. This study suggests that focal PNI is not an adverse feature.

EFFECT OF RADIOTHERAPY VOLUME AND DOSE ON SECONDARY CANCER RISK IN STAGE I TESTICULAR SEMINOMA

PURPOSE To estimate and compare the secondary cancer risk (SCR) due to para-aortic (PA), dogleg field (DLF), or extensive field (EF) radiotherapy (RT) at different dose levels for Stage I testicular seminoma. METHODS AND MATERIALS The organ equivalent dose concept with a linear, plateau, and linear-exponential dose-response model was applied to the dose distributions to estimate the SCR. The dose distributions were calculated in a voxel-based anthropomorphic phantom. Three different three-dimensional plans were computed: PA, DLF, and EF. The plans were calculated with 6-MV photons and two opposed fields, using 20 Gy in 10 fractions. RESULTS The estimated cumulative SCR for a 75-year-old patient treated with PA-RT at age 35 was 23.3% (linear model), 20.9% (plateau model), and 20.8% (linear-exponential model) compared with 19.8% for the general population. Dependent on the model, PA-RT compared with DLF-RT reduced the SCR by 48-63% or 64-69% when normalized to EF-RT. For PA-RT, the linear dose-response model predicted a decrease of 45% in the SCR, using 20 Gy instead of 30 Gy; the linear-exponential dose-response model predicted no change in SCR. CONCLUSION Our model suggested that the SCR after PA-RT for Stage I testicular seminoma is reduced by approximately one-half to two-thirds compared with DLF-RT, independent of the dose-response model. The SCR is expected to be equal or lower with 20 Gy than with 30 Gy. In the absence of mature patient data, the organ equivalent dose concept offers the best potential method of estimating the SCR when discussing treatment options with patients.