Dose-escalated radiotherapy is known to improve progression free survival in patients with localized prostate cancer, and recent advances have led to the standardization of ultrahypofractionated ...stereotactic ablative radiotherapy (SABR) delivered in just 5-fractions. Based on the known effectiveness of the accepted though invasive 2-fraction treatment method of high-dose-rate brachytherapy and given the ubiquity of prostate cancer, a further reduction in the number of treatments of external-beam SABR is possible. This study aims to evaluate the safety, efficacy, and non-inferiority of generalizable 2-fraction SABR compared to the current 5-fraction regimen.
502 patients will be enrolled on this phase II/III randomized control trial. Eligible patients will have previously untreated low- or favorable intermediate-risk adenocarcinoma of the prostate. Patients will be randomized between standard SABR of 40 Gy in 5 fractions given every-other-day and 27 Gy in 2 fractions at least two days apart but completing within seven days. MRI-based planning, radiopaque hydrogel spacer insertion, and fiducial marker placement are required, and SABR will be delivered on either a standard CT-guided linear accelerator or MR-LINAC. The primary endpoint will be freedom from disease progression, with additional secondary clinical, toxicity, and quality of life endpoints.
This study will be the largest prospective randomized trial, adequately powered to demonstrate non-inferiority, comparing 2-fraction SABR to standard 5-fraction SABR for localized prostate cancer. As the protocol does not obligate use of an MRI-LINAC or other adaptive technologies, results will be broadly generalizable to the wider community.
This trial is registered on Clinicaltrials.gov: ClinicalTrials.gov Identifier: NCT06027892.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
TTFields are a loco-regional, anti-mitotic treatment comprising low-intensity alternating electric fields. In the EF-14 study of newly diagnosed glioblastoma (ndGBM), TTFields in combination with ...temozolomide (TMZ) significantly improved survival vs. TMZ alone. In preclinical studies TTFields had a radiosensitizing effect and increased the efficacy of radiation therapy (RT). This study prospectively evaluated the feasibility and safety of TTFields administered concurrently with RT and TMZ in ndGBM patients.
Patients with histologically confirmed ndGBM were treated with TTFields/RT/TMZ followed by adjuvant TMZ/TTFields. TTFields (200 kHz) were delivered for ≥18 hours/day with transducer arrays removed during RT delivery. RT was administered to the tumor bed in 30 fractions (total dose 60 Gy) combined with daily TMZ (75 mg/m
). In the adjuvant phase, patients received monthly TMZ (150-200 mg/m
for 5 days) plus TTFields. Patients were followed for 24 months or until second disease progression. The primary outcome was safety of the combined therapies; secondary outcomes included progression-free survival (PFS) and overall survival (OS). Adverse events (AEs) were graded per CTCAE v4.0.
Ten patients were enrolled at a single center between April and December 2017. Median age was 60.2 years, median Karnofsky Performance Score was 90.0, and 80% patients were male. Five (50%) patients had undergone tumor resection while the remainder had biopsy only. Eight patients experienced ≥1 RT treatment delay; delays were unrelated to TTFields treatment. All patients experienced ≥1 AE. Three patients suffered from serious AEs (urinary tract infection, confusional state, and decubitus ulcer) that were considered unrelated to TTFields. The most common AE was skin toxicity, reported in eight (80%) patients; all were of low severity (CTCAE grade 1-2) and were reported as related to TTFields treatment. Median PFS from enrollment was 8.9 months; median OS was not reached at the time of study closure.
Eighty percent of patients experienced grade 1-2 TTFields-related skin toxicity. No other TTFields-related toxicities were observed without an increase in RT- or TMZ-related toxicities as a result of combining TTFields with these therapies. Preliminary efficacy results are promising and warrant further investigation of concurrent TTFields/RT/TMZ treatment in ndGBM patients.
Anaplastic thyroid carcinoma is an undifferentiated aggressive tumor with a high rate of regional and distant spread and a grave prognosis (median survival, 3 months) with no standardized treatment.
...To review the effect of an active treatment policy on the outcome of anaplastic thyroid carcinoma.
Retrospective comparative study of all patients diagnosed as having anaplastic thyroid carcinoma and undergoing treatment from January 1, 2008, through December 31, 2013, in a tertiary university-affiliated medical center. Data were collected by medical record review. Final follow-up was completed on November 30, 2014. Data were analyzed from December 1 to 3, 2014.
Treatment options included surgery and adjuvant concomitant radiotherapy and chemotherapy with doxorubicin hydrochloride or paclitaxel for local disease; full-dose chemoradiotherapy (70 Gy to the gross tumor) for local disease when surgery was not feasible; aggressive palliative radiotherapy (50 Gy to the gross tumor) for metastatic disease; and palliative radiotherapy (≤ 30 Gy) for metastatic disease with a low performance status.
Survival time and quality of life.
Of the 26 patients (including 15 women) who met the inclusion criteria, 11 underwent radiotherapy with curative intent. These patients included 5 who underwent curative surgery (5 with chemotherapy) and 6 who received primary chemotherapy. Nine patients received aggressive palliative radiotherapy, and 3 received palliative radiotherapy. The remaining 3 patients were not treated. Curative radiotherapy was associated with a significantly longer overall median (95% CI) survival time (11 8.1-13.9 months) than aggressive palliative radiotherapy (6 3.1-8.9 months), palliative radiotherapy (3 0.0-7.8 months), and no treatment (1 month) (P < .001). Chemotherapy in 10 patients had a significant effect on survival (mean 95% CI, 11 1.2-6.8 vs 4 8.1-13.9 months for patients who did not receive chemotherapy; P = .01). Among the patients who underwent surgery and curative radiotherapy, 3 were alive after more than 3 years of follow-up. No association of survival with patient sex (median 95% CI survival for men and women, 9 3.6-14.4 and 5 0.3-9.7 months, respectively; P = .54) or a history of thyroid disease (median 95% CI survival for those with and without, 4 1.0-6.9 and 9 5.4-12.5 months, respectively; P = .15) was found.
Anaplastic thyroid carcinoma has a grave prognosis, but an aggressive approach, including surgery, chemotherapy, and radiotherapy, seems to improve survival. Higher doses of radiotherapy may have a survival benefit in candidates for palliative treatment and may be considered for patients with extensive disease.
Objectives/Hypothesis
To assess the differences between patients with laryngeal squamous cell carcinoma under 40 years old and those 40 years old or older. A secondary objective was to compare ...survival outcome between these cohorts.
Study Design
Retrospective chart review.
Methods
We reviewed the medical charts of all patients treated in our tertiary referral center for laryngeal squamous cell carcinoma from 2005 to 2014. Patients aged < 40 years at diagnosis were compared to older patients.
Results
The study group comprised 160 patients. Of them, 13 were aged < 40 years at diagnosis. Mean age was 35 ± 3.9 years and 64.4 ± 11 years for the two groups. Among the younger patients, 38% were smokers (mean pack/day, 2.2) versus 71% in the older group (mean pack/day, 3). The younger group typically had a more advanced stage than the older group at presentation; eight young patients (62%) had stage III or IV versus 49 (33%) in the older group (P = .042). Mean overall survival was 6.7 ± 1 years for those under 40 years old and 7.7 ± 0.2 years for the older patients (P = .2). The 5‐year survival rate was 69% for young patients and 90% for the older group (P = .04). However, there was no significant between‐group difference in overall survival or 5‐year survival rate when stratified for early‐ and late‐stage disease.
Conclusions
There is a lower prevalence of classic risk factors in younger patient with laryngeal carcinoma in this study, suggesting a different etiology compared to our older cohort. The under‐40 cohort presented with more advanced disease and had a worse 5‐year survival; however, when stratified for early‐ versus late‐stage disease, there was no significant difference in overall or 5‐year survival between the groups. This may suggest that, despite a different etiology, laryngeal cancer behaves similarly in older and younger patients.
Level of Evidence
4. Laryngoscope, 128:1602–1605, 2018
Introduction Precise patient positioning with image guidance (IGRT) is essential for safe prostate radiotherapy. We present the first report of utilizing a CT-visible hydrogel spacer, used to ...decrease rectal radiation dose, as a surrogate fiducial marker to aid in daily IGRT with cone-beam CT (CBCT) in stereotactic radiotherapy (SABR) for prostate cancer. Materials and methods Prior to CT simulation, patients underwent placement of three intraprostatic gold fiducial markers and radiopaque hydrogel spacer per standard practice. At treatment, after initial setup, a CBCT was acquired and fused to the planning CT based on 3-dimensional matching of the spacer. A second alignment was then performed based on the fiducial markers. The six directional shifts (three linear and three rotational) were recorded, and the differences compared. Results 140 individual fractions across 41 consecutive patients were evaluated. Mean/median differences between hydrogel spacer-based and fiducial-based alignment in linear (vertical, longitudinal, lateral) and rotational (rotation, pitch, roll) shifts were 0.9/0.6mm, 0.8/0.5mm, and 0.6/0.4mm, and 0.38/0, 0.62/0, and 0.35/0 degrees, respectively. No difference was observed in 9.9%, 22.9%, and 22.14% of linear shifts, and 65.7%, 65%, and 66.4% rotational shifts, respectively. Significantly smaller differences were observed in the latter 70 fractions vs. the former, and results were consistent across evaluators. Conclusions For precise daily IGRT with CBCT for prostate SABR, alignment using a radiopaque hydrogel spacer was highly comparable to intraprostatic fiducial markers. This represents the first report supporting an additional indication of IGRT for a CT-visible hydrogel spacer, to further enhance treatment accuracy and potentially obviate the need for the additional fiducial marker procedure.
Placement of a perirectal hydrogel spacer has been demonstrated to reduce the risk of rectal toxicity from prostate radiation. Practices vary regarding the timing of CT simulation after hydrogel ...placement, and the ideal schedule remains unknown.
Thirty patients with localized prostate adenocarcinoma underwent transrectal ultrasound-guided placement of an iodinated SpaceOAR™ hydrogel prior to radiotherapy. Per evolving practice, 15 completed same-day simulation and 15 returned for simulation 1-2 weeks later. Hydrogel volume, perirectal distance, air-void volume, and rectal dosimetry per NRG GU005 were compared between CT simulation, 1st fraction Cone-Beam-CT (CBCT), and final CBCT.
CT simulation occurred 8.8 ± 2.4 days after placement in the delayed group, with no significant difference in the interval between simulation and 1st fraction between groups (
= 0.165). Greater observed de-creases in hydrogel volume (0.57 cc
0.04 cc,
= 0.0002), and perirectal distance at both mid-gland (1.32 mm
0.17 mm) and tallest point (2.40 mm
0.04 mm) were seen on 1st-fraction CBCT in the same-day group (
= 0.0039;
= 0.0002). Per dosimetry recalculated on 1st fraction CBCT, five (D3 cc and D50%) versus one (D50%) rectal dose parameters were exceeded in the same-day and delayed groups, respectively, and 10 versus one parameters had a relative increase of ≥ 20%.
Due to the evolving anatomic changes in the days following hydrogel placement, same-day simulation scanning may introduce unintended variability in rectal dosimetry at the time of prostate radiotherapy.
The objective of this study was to review and assess the impact of additional induction chemotherapy to concomitant chemoradiation in head and neck squamous cell cancer. We performed a comparative ...systematic review and meta-analysis of clinical trials of induction chemotherapy + chemoradiation and chemoradiation alone in this setting. We identified trials randomizing 1314 patients (published 2004-2015). A non-statistically significant trend was observed in favor of induction chemotherapy + chemoradiation on overall survival (hazard ratio, 0.88; 95% confidence interval, 0.75-1.04). Disease control was superior in the induction chemotherapy + chemoradiation group (hazard ratio, 0.69; 95% confidence interval, 0.57-0.83). The rate of complete response improved with induction chemotherapy compared with concomitant chemoradiation (relative risk, 1.52; 95% confidence interval, 1.20-1.92). This study showed no benefit of induction chemotherapy + chemoradiation on overall survival. However, improved complete response rate and death certificate-only registrations may imply that selected patients may benefit from induction chemotherapy.
Genomic research of high grade glioma (HGG) has revealed complex biology with potential for therapeutic impact. However, the utilization of this information and impact upon patient outcome has yet to ...be assessed. We performed capture-based next generation sequencing (NGS) genomic analysis assay of 236/315 cancer-associated genes, with average depth of over 1000 fold, to guide treatment in HGG patients. We reviewed clinical utility and response rates in correlation to NGS results. Forty-three patients were profiled: 34 glioblastomas, 8 anaplastic astrocytomas, and one patient with anaplastic oligodendroglioma. Twenty-five patients were profiled with the 315 gene panel. The median number of identified genomic alterations (GAs) per patient was 4.5 (range 1–23). In 41 patients (95 %) at least one therapeutically-actionable GA was detected, most commonly in
EGFR
17 (40 %). Genotype-directed treatments were prescribed in 13 patients, representing a 30 % treatment decision impact. Treatment with targeted agents included everolimus as a single agent and in combination with erlotinib; erlotinib; afatinib; palbociclib; trametinib and BGJ398. Treatments targeted various genomic findings including
EGFR
alterations,
mTOR
activation, cell cycle targets and
FGFR1
mutations. None of the patients showed response to respective biologic treatments. In this group of patients with HGG, NGS revealed a high frequency of GAs that lead to targeted treatment in 30 % of the patients. The lack of response suggests that further study of mechanisms of resistance in HGG is warranted before routine use of biologically-targeted agents based on NGS results.
Acute lymphoblastic leukemia (ALL) is a malignant neoplasm of the blood stem cells, characterized by increased formation of immature lymphocytes. Ocular manifestations may vary with ocular, adnexal, ...and orbital involvement. In this case report, we describe the first case of extramedullary relapse of ALL limited to the anterior chamber of the eye treated with the novel chimeric antigen receptor T (CAR T)-cell therapy and provide a literature review of cases of ALL relapse in the anterior chamber. A 21-year-old male with a history of B-cell ALL presented with a unilateral blurry vision in his left eye. Ocular examination revealed the presence of cells +3 in the anterior chamber and a 1.5-mm hypopyon. Anterior chamber aspiration confirmed a B-ALL relapse. The patient was successfully treated with radiotherapy of his left eye and received CTL-019 transduced T cells (tisagenlecleucel; Novartis) with cytarabine as a bridging chemotherapy treatment. On the last examination, 18 months after the first presentation, the patient presented a complete ocular remission with no systemic or CNS involvement. ALL relapse may involve the anterior chamber of the eye, and an accurate diagnosis is crucial to enable a fast and appropriate treatment. Novel CAR T-cell immunotherapy, combined with ocular irradiation, may be considered in such cases.
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