Radiotherapy as nose preservation treatment strategy for cancer of the nasal vestibule: The Dutch experience.

BACKGROUND AND PURPOSE: Primary radiotherapy is often preferred for early-stage cancer of the nasal vestibule (CNV), combining high disease control with preservation of nasal anatomy. However, due to practice variation and an absence of comparative trials, no consensus exists on preference for brachytherapy (BT) or external beam radiotherapy (EBRT). We compared these modalities in terms of disease control, nose preservation rates and toxicity. MATERIALS AND METHODS: Medical records of 225 patients with T1-T2 squamous cell carcinoma of the nasal vestibule treated with 3D image-guided primary radiotherapy between Jan 2010 and Dec 2016 in 6 Dutch institutions were reviewed retrospectively. RESULTS: 153 of 225 patients were treated with BT, 65 with EBRT and 7 with other modalities. Median follow-up was 46 months. Overall 3-year local control (LC) and regional control (RC) were 87% and 89%. Five-year disease-specific survival (DSS) and overall survival (OS) were 94% and 82%. Three-year survival with preserved nose (SPN) was 76%. BT provided higher 3-year LC (95% vs 71%, p < 0.01) and SPN compared with EBRT (82% vs 61%, p < 0.01). Multivariable and propensity-score-matched cohort analyses confirmed better outcomes after BT. No difference was seen in DSS or OS. Five-year incidence of CTCAE 5.0 grade ≥2 toxicity was higher after BT (20% vs 3%, p = 0.03) and consisted mostly of radiation ulcers. 50% of all late toxicity recovered. CONCLUSION: In this largest-to-date multicenter analysis of T1-T2 CNV, BT achieved superior LC and SPN compared with EBRT. Grade 1-2 radiation ulcers occurred more frequently after brachytherapy, but were transient in half the cases. Considering these results, BT can be recommended as first-line treatment for T1-T2 CNV.

Treatment of head and neck carcinoma of unknown primary: Cracking a nut with a sledgehammer?

OBJECTIVES: To compare the impact on survival and late radiation toxicity of patients with squamous cell carcinoma of unknown primary who were treated with ipsilateral neck dissection and ipsilateral postoperative radiotherapy (PORT) and patients treated with ipsilateral neck dissection and PORT to both sides of the neck plus the pharyngeal axis. METHODS: Retrospective cohort study performed at the Erasmus University Medical Center in which 78 patients with squamous cell carcinoma of unknown primary were identified. Thirty-nine patients received PORT to both sides of the neck plus the pharyngeal axis (BILAX) and another 39 patients were irradiated on the ipsilateral neck (IPSI) only. The endpoints of the present study were 3-year overall survival (OS), 3-year disease-free survival (DFS), and overall late radiation toxicity. RESULTS: The 3-year OS rate of the entire group of 78 patients was 74.2% and the 3-year DFS rate was 72.7%. The 3-year OS rates for the IPSI and the BILAX groups were 74.4% and 74.1%, respectively (P = .654). The most common late radiation toxicity experienced was xerostomia (64.8%), which was significantly more often seen in the BILAX group than in the IPSI group (83.8% and 44.1%, respectively, P = .001). Overall late radiation toxicity was significantly higher in the BILAX group (P = .003). CONCLUSION: There was no significant difference in OS and DFS rates between the IPSI and the BILAX group. Late radiation toxicity was significantly higher in the BILAX group. LEVEL OF EVIDENCE: Level 2b: Individual retrospective cohort study.

Interstitial radiation therapy for early-stage nasal vestibule cancer: a continuing quest for optimal tumor control and cosmesis.

INTRODUCTION: This article reports on the effectiveness, cosmetic outcome, and costs of interstitial high-dose-rate (HDR) brachytherapy for early-stage cancer of the nasal vestibule (NV) proper and/or columella high-dose-rate (HDR). METHODS AND MATERIALS: Tumor control, survival, cosmetic outcome, functional results, and costs were established in 64 T1/T2N0 nasal vestibule cancers treated from 1991-2005 by fractionated interstitial radiation therapy (IRT) only. Total dose is 44 Gy: 2 fractions of 3 Gy per day, 6-hour interval, first and last fraction 4 Gy. Cosmesis is noted in the chart by the medical doctor during follow-up, by the patient (visual analog scale), and by a panel. Finally, full hospital costs are computed. RESULTS: A local relapse-free survival rate of 92% at 5 years was obtained. Four local failures were observed; all four patients were salvaged. The neck was not treated electively; no neck recurrence in follow-up was seen. Excellent cosmetic and functional results were observed. With 10 days admission for full treatment, hospital costs amounted to euro5772 (7044 US dollars). CONCLUSION: Excellent tumor control, cosmesis, and function of nasal airway passage can be achieved when HDR-IRT for T1/T2N0 NV cancers is used. For the more advanced cancers (Wang classification: T3 tumor stage), we elect to treat by local excision followed by a reconstructive procedure. The costs, admission to hospital inclusive, for treatment by HDR-IRT amounts to euro5772 (7044 US dollars). This contrasts substantially with the full hospital costs when NV cancers are treated by plastic reconstructive surgery, being on average threefold as expensive.

Application of the No Action Level (NAL) protocol to correct for prostate motion based on electronic portal imaging of implanted markers.

PURPOSE: To evaluate the efficacy of the No Action Level (NAL) off-line correction protocol in the reduction of systematic prostate displacements as determined from electronic portal images (EPI) using implanted markers. METHODS AND MATERIALS: Four platinum markers, two near the apex and two near the base of the prostate, were implanted for localization purposes in patients who received fractionated high dose rate brachytherapy. During the following course of 25 fractions of external beam radiotherapy, the position of each marker relative to the corresponding position in digitally reconstructed radiographs (DRRs) was measured in EPI in 15 patients for on average 17 fractions per patient. These marker positions yield the composite displacements due to both setup error and internal prostate motion, relative to the planning computed tomography scan. As the NAL protocol is highly effective in reducing systematic errors (recurring each fraction) due to setup inaccuracy alone, we investigated its efficacy in reducing systematic composite displacements. The analysis was performed for the center of mass (COM) of the four markers, as well as for the cranial and caudal markers separately. Furthermore, the impact of prostate rotation on the achieved positioning accuracy was determined. RESULTS: In case of no setup corrections, the standard deviations of the systematic composite displacements of the COM were 3-4 mm in the craniocaudal and anterior-posterior directions, and 2 mm in the left-right direction. The corresponding SDs of the random displacements (interfraction fluctuations) were 2-3 mm in each direction. When applying a NAL protocol based on three initial treatment fractions, the SDs of the systematic COM displacements were reduced to 1-2 mm. Displacements at the cranial end of the prostate were slightly larger than at the caudal end, and quantitative analysis showed this originates from left-right axis rotations about the prostate apex. Further analysis revealed that significant time trends are present in these prostate rotations. No significant trends were observed for the prostate translations. CONCLUSIONS: The NAL protocol based on marker positions in EPI halved the composite systematic displacements using only three imaged fractions per patient, and thus allowed for a significant reduction of planning margins. Although large rotations of the prostate, and time trends therein, were observed, the net impact on the measured displacements and on the accuracy obtained with NAL was small.

Toxicity and quality of life after high-dose-rate brachytherapy as monotherapy for low- and intermediate-risk prostate cancer.

BACKGROUND AND PURPOSE: The use of HDR brachytherapy (HDR-BT) as monotherapy for prostate cancer (PC) is increasing worldwide with good tumour control rates and acceptable toxicity. We report our results on toxicity and quality of life (QoL) after HDR-BT monotherapy for PC patients. MATERIALS AND METHODS: 166 low- and intermediate-risk localized PC patients were treated with HDR-BT to a total dose of 38Gy in four fractions. Genitourinary (GU) and gastrointestinal (GI) toxicities were prospectively assessed using EORTC-RTOG questionnaires and physicians charts. QoL was evaluated using EORTC QLQ-PR25 questionnaires. RESULTS: Three months after treatment, acute GU and GI toxicities were reported in 10.8% and 7.2%. Acute toxicity resolved within two months in the majority of patients (61%). Late grade ⩾ 2 GU and GI toxicity were reported in 19.7% and 3.3% of patients 12 months after HDR-BT. Mean QLQ-PR25 scores showed clinically relevant changes from baseline for urinary symptoms and sexual functioning. With a mean follow-up of 35 months, biochemical failure was observed in 2.4%. Overall survival at 60 months was 93.6% and cancer-specific survival was 100%. CONCLUSIONS: HDR-BT monotherapy for localized PC showed excellent clinical outcome and acceptable acute and late toxicity. Urinary symptoms and sexual function QoL decreased after treatment.

Impact of volume and location of irradiated rectum wall on rectal blood loss after radiotherapy of prostate cancer.

PURPOSE: To identify dose-volume parameters related to late rectal bleeding after radiotherapy for prostate cancer. MATERIALS AND METHODS: Clinical complication data from a randomized trial were collected and linked to the individual dose-volume data. In this trial, patients with prostate cancer were treated with either conventional (with rectangular fields) or three-dimensional conformal radiotherapy to a dose of 66 Gy. Patient complaints, including rectal blood loss, were collected for 199 patients, using questionnaires. Absolute and relative dose-volume histograms (DVHs) of the rectal wall (with and without the anal region) were calculated with and without rectal filling. A proportional hazard regression (PHR) model was applied to estimate the probability of any rectal blood loss within 3 years, as a function of several DVH parameters. In a multivariable analysis, dose-volume parameters were tested together with patient- and treatment-related parameters (age, smoking, diabetes, cardiovascular disease, tumor stage, neo-adjuvant androgen deprivation, conformal vs. conventional and rectal bleeding during treatment). RESULTS: The estimated incidence of any and moderate/severe rectal bleeding at 3 years was 33% and 8%, respectively. Differences between the conventional and conformal technique were small and not significant. The analysis of relative DVHs of the rectal wall (with and without the anal region), showed significant (p < 0.01) relations between the irradiated volume and the probability of rectal blood loss within 3 years for dose levels between 25 Gy and 60 Gy. This relationship was shown in subgroups defined by dose-volume cutoff points as well as in the PHR model, in which a continuously rising risk was seen with increasing volumes. For absolute DVHs and DVHs of the rectum including filling, less or no significant results were observed. The most significant volume-effect relation (p = 0.002) was found at 60 Gy for the rectum wall excluding the anal region. The probability of rectal bleeding increased from 10% to 63% when the irradiated rectum volume at 60 Gy increased from 25% to 100%. Other factors. including age, smoking, diabetes, cardiovascular disease, tumor stage, neo-adjuvant androgen deprivation, conformal vs. conventional, rectal bleeding during treatment, rectum length. and whole rectum volume. did not have a significant effect in the multivariable analysis. When controlling for the volumes at 60 Gy, the volumes at lower dose levels (25-55 Gy) were no longer significant (p = 0.5). CONCLUSIONS: For any rectal bleeding within 3 years, an overall incidence of 33% was observed for patients treated to 66 Gy. For this endpoint, a volume-effect relation was found for DVH parameters of the relative rectal wall volume. This relationship appeared to be most significant for the rectum without the anal region and for the higher dose levels (50-60 Gy).

Anatomy based inverse planning in HDR prostate brachytherapy.

The purpose of this study is to evaluate anatomy based inverse planning as implemented in PLATO BPS 14.2 for planning of HDR prostate implants. Six patients were analysed. The dose distributions were optimized using geometric optimization followed by graphical optimization (GO), anatomy based inverse planning or standard inverse optimization (SIO), tuned inverse optimization (TIO) and tuned inverse optimization followed by graphical optimization (GOTIO). The mean target coverage was 93+/-4%, 53+/-11%, 74+/-8%, 90+/-3%, respectively, for GO, SIO, TIO and GOTIO. The conformal index COIN was 0.74+/-0.02, 0.43+/-0.15 and 0.77+/-0.07, respectively, for GO, SIO and GOTIO. Improved dose homogeneity was found when comparing GOTIO with GO.

High relapse-free survival after preoperative and intraoperative radiotherapy and resection for sulcus superior tumors.

STUDY OBJECTIVES: Relapse-free survival in patients with sulcus superior tumors. DESIGN: Prospective registration study. SETTING: Department of surgical oncology of a university hospital. PATIENTS: Twenty-one patients treated with preoperative radiotherapy (46 Gy), lobectomy and chest-wall resection, and intraoperative radiotherapy (10 Gy). RESULTS: After a median follow-up of 18 months, 18 patients (85%) were free from locoregional relapse, while 8 patients were still alive. CONCLUSIONS: The results show that this protocol can achieve excellent local tumor control and can even be used for palliative treatment.

Radical radiotherapy compared with surgery for advanced squamous cell carcinoma of the base of tongue.

PURPOSE: This study reports on T3/T4 base of tongue (BOT) tumors treated at the Erasmus MC (Rotterdam) with external beam radiotherapy (EBRT) and brachytherapy (BT). Local control, survival, and functional outcome are compared to results obtained in similar patients treated at the Vrije University Medical Center (VUMC, Amsterdam) by surgery and postoperative RT (PORT). METHODS AND MATERIALS: At Rotterdam 46/2 Gy was given to the primary and bilateral neck, followed by an implant using low-dose-rate (LDR 24-35 Gy; median 27 Gy), or fractionated high-dose-rate (fr. HDR 20-28 Gy; median 24 Gy). A neck dissection (ND) was performed in case of N+ disease. 67% of BOT tumors had a T4 cancer. At Amsterdam surgery (S) followed by PORT 40-70 Gy (median 60 Gy) was performed; 26% BOT tumors were T4. Sex, age and nodal distribution were similar. Actuarial local control and survival were computed. Performance Status Scale (PSS) scores were established. Xerostomis was determined on visual analog scales (VAS). RESULTS: Local failure at 5-years was 37% (Rotterdam) vs. 9% (Amsterdam) (p < 0.01). The overall survival was not significantly different (median 2.5 years vs. 2.9 years, respectively [p = 0.47]). The PSS favored brachytherapy. Both groups were equally affected by xerostomia. CONCLUSIONS: The 5-year local control was 65% with EBRT and BT. This result is strongly affected by 4 patients with residual disease after implantation. The Rotterdam patients had more advanced BOT tumors (67% vs. 26% T4), explaining the higher local failure rate. Given the organ preservation properties of radiotherapy-only and the better PSS scores, the jury is still out on the optimal treatment for BOT tumors.

High-dose-rate brachytherapy and external-beam radiotherapy for hormone-naïve low- and intermediate-risk prostate cancer: a 7-year experience.

PURPOSE: To report clinical outcomes and early and late complications in 264 hormone-naïve patients with low- and intermediate-risk prostate cancer treated with high-dose-rate brachytherapy (HDR-BT) in combination with external-beam radiotherapy (EBRT). METHODS AND MATERIALS: Between February 2000 and July 2007, 264 patients underwent HDR-BT in combination with EBRT as a treatment for their low- to intermediate-risk prostate cancer. The HDR-BT was performed using ultrasound-based implantation. The total HDR-BT dose was 18 Gy in 3 fractions within 24 h, with a 6-h minimum interval. The EBRT started 2 weeks after HDR-BT and was delivered in 25 fractions of 1.8 Gy to 45 Gy within 5 weeks. RESULTS: After a mean follow-up of 74.5 months, 4 patients (1.5%) showed prostate-specific antigen progression according to the American Society for Radiation Oncology definition and 8 patients (3%) according to the Phoenix definition. A biopsy-proven local recurrence was registered in 1 patient (0.4%), and clinical progression (bone metastases) was documented in 2 patients (0.7%). Seven-year actuarial freedom from biochemical failure was 97%, and 7-year disease-specific survival and overall survival were 100% and 91%, respectively. Toxicities were comparable to other series. CONCLUSIONS: Treatment with interstitial HDR-BT plus EBRT shows a low incidence of late complications and a favorable oncologic outcome after 7 years follow-up.