Etienne Martin

Clinical impact of margin reduction on late toxicity and short-term biochemical control for patients treated with daily on-line image guided IMRT for prostate cancer.

To evaluate the impact of PTV reduction when delivering image-guided IMRT (IG-IMRT) for patients with prostate cancer. Between 2001 and 2007, 165 men were treated with daily IG-IMRT using a 3D ultrasound-based system. Median dose prescribed to the prostate was 78 Gy [74 Gy-78 Gy]. Patients were stratified regarding the CTV to the PTV margin: group A (n=87)=5mm or group B (n=78)=10mm. Late toxicity was scored using the CTC v3.0 scale. Biochemical progression-free survival (bPFS) was calculated using the Phoenix definition. Grade 2 genitourinary toxicity was 7.0% for group A and 6.6% for group B (p=1.00). Grade 2 gastrointestinal toxicity was 1.2% and 2.6% (p=0.38). With a median follow-up of 38.3 months [5.25-87.3], bPFS at 3 years was 92.5% [82.4%-96.9%] in group A and 94.3% [85.5%-97.8%] in group B (p=0.84). IG-IMRT yielded very low rates of late toxicity. Margin had impact neither on short-term bPFS nor late toxicity.

Salvage reirradiation for locoregional failure after radiation therapy for prostate cancer: who, when, where and how?

Even in the current era of dose-escalated radiotherapy for prostate cancer, biochemical recurrence is not uncommon. Furthermore, biochemical failure is not specific to the site of recurrence. One of the major challenges in the management of prostate cancer patients with biochemical failure after radiotherapy is the early discrimination between those with locoregional recurrence only and those with metastatic disease. While the latter are generally considered incurable, patients with locoregional disease may benefit from emerging treatment options. Ultimately, the objective of salvage therapy is to control disease while ensuring minimal collateral damage, thereby optimizing both cancer and toxicity outcomes. Advances in functional imaging, including multiparametric prostate MRI, abdominopelvic lymphangio-MRI, sentinel node SPECT-CT and/or whole-body PET/CT have paved the way for salvage radiotherapy in patients with local recurrence, microscopic nodal disease limited to the pelvis or oligometastatic disease. These patients may be considered for salvage reirradiation using different techniques: prostate low-dose or high-dose rate brachytherapy, pelvic and/or lomboaortic image-guided radiotherapy with elective nodal irradiation, focal nodal or bone stereotactic body radiation therapy (SBRT). An individualized approach is recommended. The decision about which treatment, if any, to use will be based on the initial characteristics of the disease, relapse patterns and the natural history of the rising prostate specific antigen (PSA). Preliminary results suggest that more than 50% of patients who have undergone salvage reirradiation are biochemically relapse-free with very low rates of severe toxicity. Large prospective studies with a longer follow-up are needed to confirm the promising benefit/risk ratio observed with salvage brachytherapy and or salvage nodal radiotherapy and/or bone oligometastatic SBRT when compared with life-long palliative hormones.

Does gap-free intensity modulated chemoradiation therapy provide a greater clinical benefit than 3D conformal chemoradiation in patients with anal cancer?

BackgroundChemoradiation is the standard treatment for anal cancer. 3D conformal radiotherapy (3D-CRT) is usually split in 2 sequences with a therapeutic break (gap) in between. Intensity-modulated radiation therapy (IMRT) makes it possible to reduce treatment time by abandoning this gap. The purpose of this study was to compare outcomes and toxicities in patients treated with either IMRT or 3D-CRT.MethodsBetween 2004 and 2011, the data of 51 patients treated with exclusive radiotherapy with or without concomitant chemotherapy for non-metastatic anal carcinoma were retrospectively analyzed. Twenty-seven patients were treated with 3D-CRT and 24 patients with IMRT, with a median dose delivered to the tumor of 59.4Gy [30.6-66.6], whatever the radiotherapy technique (p= 0.99). The median follow-up was 40 months [26.4-51.6].ResultsThere was no difference between the two groups for response to treatment (p= 0.46). Two-year overall survival, locoregional relapse-free survival and colostomy-free survival rates were 88.5%, 63% and 60.3%, respectively for the IMRT group and 81%, 76.5% and 81.1% for the 3D-CRT group (all NS). Ten patients (37%) in 3D-CRT and 11 patients (45.8%) in IMRT (p= 0.524) had grade 3 acute toxicity. No grade 4 toxicity occurred.ConclusionsOur study suggests that further investigations concerning the use of IMRT to treat cancer of the anus are warranted. IMRT makes it possible to remove the gap, but with no impact on the prognosis. Nonetheless, a longer follow-up is essential to determine whether or not IMRT has an impact on late toxicity, local control and survival compared with conventional 3D-CRT.

Pattern of occult nodal relapse diagnosed with 18F-fluoro-choline PET/CT in prostate cancer patients with biochemical failure after prostate-only radiotherapy

INTRODUCTION The purpose of this study was to describe the pattern of nodal relapse with (18)F-fluoro-choline (FCH) Positron Emission Tomography/Computerized Tomography (PET/CT) in prostate cancer patients after radiotherapy. MATERIALS AND METHODS Eighty-three patients had a FCH PET/CT at time of biochemical failure. Of 65 patients with positive findings, 33 had positive nodes. This analysis included 31 patients who had undergone prior prostate-only radiotherapy with or without a prior radical prostatectomy. Each FCH positive node was assigned to a lymph node station with respect to the CTV defined by the RTOG guidelines (CTVRTOG). 3D mapping was performed after each node was manually placed in a reference planning CT scan after automatic co-registration of the two scans based on bone anatomy. Eighteen patients (58%) underwent focal salvage FCH PET-guided stereotactic radiotherapy with no hormones. RESULTS Fourteen patients (45.2%) had a relapse outside the CTVRTOG. Of the 17 patients with a positive node inside the CTVRTOG, 15 had a single node (88.2%) while seven patients out of the 13 evaluable patients (53.9%) who had a relapse outside the CTVRTOG had ⩾2 positive nodes on FCH PET/CT (OR=8.75, [95% CI: 1.38-54.80], p=0.020). Relapses that occurred outside the CTVRTOG involved the proximal common iliac (19.3%) and lower periaortic nodes (19.3%) up to L2-L3. CONCLUSION 3D mapping of nodal relapses evaluated with FCH PET/CT suggests that with IMRT the upper field limit of pelvic radiotherapy could be extended to L2-L3 safely to cover 95% of nodal stations at risk of an occult relapse.

Radiothérapie guidée par l’image des cancers prostatiques : concepts et implications

Intensity modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) are technological developments, which when applied in a model of prostate cancer, led to a significant reduction in the toxicity and digestive and urinary sequelae of 3D conformational radiotherapy. The major clinical benefits of these techniques with regard to reduced digestive and urinary toxicity are unequivocal since very few sequelae have been reported at 10 years (2% of grade 2 and 1% of grade 3 digestive toxicity; 11% of grade 2 and 5% of grade 3 urinary toxicity). Even when these two techniques are combined, IG-IMRT significantly diminishes late genitourinary toxicity. In the absence of adaptive radiotherapy, there are many IGRT protocols and repositioning techniques, and every step in the IGRT process must be carried out with extreme rigor: installing the patient and contention system, repositioning technique with or without fiduciary markers, type of repositioning imaging, definition of margins inherent in each technique (prostate, seminal vesicles and/or pelvic lymph nodes), frequency of repositioning during treatment, dietary constraints with or without rectal lavage. For these reasons, every centre that performs IGRT must carefully and rigorously assess the uncertainties of repositioning linked to the IGRT technique. In this review, we analyzed data from the literature based on dosimetric studies and the proven clinical impact in order to answer the different questions asked by radiation oncologists at every step of the IGRT process for cancer of the prostate. Recommendations are made for the repositioning protocols according to the most widely used repositioning techniques: fiduciary markers or soft tissues, kV-CBCT or MV-CBCT, 3D ultrasonography.

Primary liver cancer

Due to its increasing incidence and a grim prognosis, primary liver cancer remains a diagnostic and therapeutic challenge. For small localized tumors, surgical resection and liver transplantation are standard treatments with a curative-intent. Therapeutic options for locally advanced or metastatic diseases are limited. Globally, surgery fits less than 20% of patients. Early detection in high-risk patients and prevention of risk factors remain the key points in the standard care. External radiotherapy is a non invasive treatment with encouraging results for non operable patients. Emerging stereotactic radiotherapy yields high rates of local control without compromising toxicity. Tumors with bad prognostic factors could be cured with this approach.

Docetaxel-titanate nanotubes enhance radiosensitivity in an androgen-independent prostate cancer model

Around 40% of high-risk prostate cancer patients who undergo radiotherapy (RT) will experience biochemical failure. Chemotherapy, such as docetaxel (DTX), can enhance the efficacy of RT. Multidrug resistance mechanisms often limit drug efficacy by decreasing intracellular concentrations of drugs in tumor cells. It is, therefore, of interest to develop nanocarriers of DTX to maintain the drug inside cancer cells and thus improve treatment efficacy. The purpose of this study was to investigate the use of titanate nanotubes (TiONts) to develop a TiONts-DTX nanocarrier and to evaluate its radiosensitizing in vivo efficacy in a prostate cancer model. In vitro cytotoxic activity of TiONts-DTX was evaluated using an MTS assay. The biodistribution of TiONts-DTX was analyzed in vivo by single-photon emission computed tomography. The benefit of TiONts-DTX associated with RT was evaluated in vivo. Eight groups with seven mice in each were used to evaluate the efficacy of the nanohybrid combined with RT: control with buffer IT injection ± RT, free DXL ± RT, TiONts ± RT and TiONts-DXL ± RT. Mouse behavior, health status and tumor volume were monitored twice a week until the tumor volume reached a maximum of 2,000 mm3. More than 70% of nanohybrids were localized inside the tumor 96 h after administration. Tumor growth was significantly slowed by TiONts-DTX associated with RT, compared with free DTX in the same conditions (P=0.013). These results suggest that TiONts-DTX improved RT efficacy and might enhance local control in high-risk localized prostate cancer.

Multiparametric MRI and post implant CT-based dosimetry after prostate brachytherapy with iodine seeds: The higher the dose to the dominant index lesion, the lower the PSA bounce

PURPOSE To determine whether post-implant MRI-based dosimetry of the Dominant Intra-prostatic Lesion (DIL) could best predict the occurrence of PSA bounce after prostate brachytherapy. METHODS AND MATERIALS We selected 66 patients with a low risk prostate cancer treated with (125)I prostate brachytherapy as monotherapy. Post-implant dosimetry based on day 30 CT-scan and multiparametric MRI co-registration was generated: planned D90, D95, V100, V150 values were calculated for each DIL. Bounce was defined as a PSA elevation ⩾ 0.2 ng/mL from the previous baseline value followed by a decrease to or below the prior nadir with no additional treatment. RESULTS After a median follow-up of 35.5 months (range 13.2-72.5), a PSA bounce occurred in 24 (36.4%) patients. The mean planned D90 of the DIL was significantly lower in bouncers: 196 ± 61 Gy vs. 234 ± 62 Gy, p = 0.018. The mean planned V150 of the DIL was 56 ± 32% for bouncers while it was 75 ± 30% for non-bouncers, p = 0.026. CONCLUSION A lower planned D90 or V150 in the DIL were predictive of PSA bounce after prostate brachytherapy. PSA bounce could be caused by delayed cell death related to sublethal damage accumulation in the tumor.

Exclusive image guided IMRT vs. radical prostatectomy followed by postoperative IMRT for localized prostate cancer: a matched-pair analysis based on risk-groups

BackgroundTo investigate whether patients treated for a localized prostate cancer (PCa) require a radical prostatectomy followed by postoperative radiotherapy or exclusive radiotherapy, in the modern era of image guided IMRT.Methods178 patients with PCa were referred for daily exclusive image guided IMRT (IG-IMRT) using an on-line 3D ultra-sound based system and 69 patients were referred for postoperative IMRT without image guidance after radical prostatectomy (RP + IMRT). Patients were matched in a 1:1 ratio according to their baseline risk group before any treatment. Late toxicity was scored using the CTV v3.0 scale. Biochemical failure was defined as a postoperative PSA ≤ 0.1 ng/mL followed by 1 consecutive rising PSA for the postoperative group of patients and by the Phoenix definition (nadir + 2 ng/mL) for the group of patients treated with exclusive radiotherapy.ResultsA total of 98 patients were matched (49:49). From the start of any treatment, the median follow-up was 56.6 months (CI 95% = [49.6-61.2], range [18.2-115.1]). No patient had late gastrointestinal grade ≥ 2 toxicity in the IG-IMRT group vs. 4% in the RP + IMRT group. Forty two percent of the patients in both groups had late grade ≥ 2 genitourinary toxicity. The 5-year FFF rates in the IG-IMRT group and in the RP + IMRT groups were 93.1% [80.0-97.8] and 76.5% [58.3-87.5], respectively (p = 0.031).ConclusionsPatients with a localized PCa treated with IG-IMRT had better oncological outcome than patients treated with RP + IMRT. Further improvements in postoperative IMRT using image guidance and dose escalation are urgently needed.

Time interval between surgery and start of adjuvant radiotherapy in patients with soft tissue sarcoma: A retrospective analysis of 1131 cases from the French Sarcoma Group

PURPOSE The aim of this study was to evaluate the impact of the time interval (TI) between surgery and adjuvant radiotherapy (RT) in soft tissue sarcoma (STS). METHODS AND MATERIALS Data from 1131 patients treated between 1990 and 2014 were retrospectively reviewed. Inclusion criteria were: limb or superficial trunk wall STS (R0 or R1 resection) and adjuvant RT. The impact of TI on 10-year local relapse-free survival (LRFS) and 10-year overall survival (OS) was analyzed using a Log-rank test and then Cox Model. RESULTS The median TI was 82days (range, 18-346). With a median follow-up of 235months (range, 2-296months), the 10-year LRFS was 57.5% (±2%) and the 10-year OS was 64.2% (±2%). With a TI of 19-39days, 40-79days, 80-119days, and ⩾120days, 10-year LRFSs were 65.3%, 55.5%, 56.9% and 61.2% (p=0.465), and 10-year OSs were 72.8%, 60.7%, 66.4% and 62.1% (p=0.347), respectively. After adjustment for the factors significantly (p⩽0.05) associated with LRFS and OS, TI did not alter LRFS (p=0.182) either OS (p=0.335). CONCLUSIONS In this retrospective STS database study, the TI between surgery and start of adjuvant RT did not seem to affect outcomes.