Purpose To evaluate the association between dynamic contrast material-enhanced (DCE) and diffusion-weighted (DW) magnetic resonance (MR) imaging with pathologic complete response after preoperative ...combined chemotherapy and radiation therapy for cervical carcinoma and evaluate the risk of local recurrence. Materials and Methods The institutional ethics committee approved the study and waived the requirement to obtain informed consent. The study comprised 52 patients with locally advanced carcinoma, treated first with combined chemotherapy and radiation therapy, who underwent MR imaging before final surgery between June 2011 and July 2015. Three radiologists evaluated conventional, DW, and DCE MR images to identify a complete response. The standard of reference was surgical-pathologic findings. Results An initial increase in signal intensity on DCE MR images that was greater in the cervical lesion than in the myometrium was defined as time-signal intensity curve type B and showed a significant association with incomplete response (P = .0004). DCE MR imaging parameters (ie, maximum slope enhancement, area under the gadolinium concentration-time curve during the first 90 seconds after gadolinium injection AUGC90, and volume transfer constant K
) and a low signal intensity on apparent diffusion coefficient (ADC) maps were significantly associated with an incomplete response (P = .027, P = .041, P = .037, and P = .032, respectively). A mean ADC of 0.0014 m
/sec or less (hazard ratio HR = 8.3), low ADC signal intensity (HR = 7.3), high signal intensity at DW imaging (HR = 7.1), and time-signal intensity curve type B (HR = 4.3) were associated with earlier recurrence (P < .05). Excellent agreement between readers was found for time-signal intensity curve analysis (κ > 0.9) and the following parameters: AUGC90, K
, and maximum slope enhancement (intraclass correlation coefficient, >0.9). Conclusion DCE MR imaging parameters, especially the time-signal intensity curve, and DW imaging are associated with complete response and incomplete response and could potentially help oncologists with management decisions. Moreover, DCE and DW MR imaging could help oncologists accentuate the follow-up for patients with a high risk of local recurrence to assess for recurrence.
RSNA, 2017 Online supplemental material is available for this article.
Concurrent chemoradiotherapy (CRT) with blockade of the PD-1 pathway may enhance immune-mediated tumor control through increased phagocytosis, cell death, and antigen presentation. The NiCOL phase 1 ...trial (NCT03298893) is designed to determine the safety/tolerance profile and the recommended phase-II dose of nivolumab with and following concurrent CRT in 16 women with locally advanced cervical cancer. Secondary endpoints include objective response rate (ORR), progression free survival (PFS), disease free survival, and immune correlates of response. Three patients experience grade 3 dose-limiting toxicities. The pre-specified endpoints are met, and overall response rate is 93.8% 95%CI: 69.8-99.8% with a 2-year PFS of 75% 95% CI: 56.5-99.5%. Compared to patients with progressive disease (PD), progression-free (PF) subjects show a brisker stromal immune infiltrate, higher proximity of tumor-infiltrating CD3
T cells to PD-L1
tumor cells and of FOXP3
T cells to proliferating CD11c
myeloid cells. PF show higher baseline levels of PD-1 and ICOS-L on tumor-infiltrating EMRA CD4
T cells and tumor-associated macrophages, respectively; PD instead, display enhanced PD-L1 expression on TAMs, higher peripheral frequencies of proliferating Tregs at baseline and higher PD-1 levels at week 6 post-treatment initiation on CD4 and CD8 T cell subsets. Concomitant nivolumab plus definitive CRT is safe and associated with encouraging PFS rates. Further validation in the subset of locally advanced cervical cancer displaying pre-existing, adaptive immune activation is warranted.
To evaluate the benefit of prophylactic inguinal irradiation (PII) in anal canal squamous cell carcinoma (ASCC).
This retrospective study analyzed the outcome of 208 patients presenting with ASCC ...treated between 2000 and 2004 in four cancer centers of the south of France.
The population study included 35 T1, 86 T2, 59 T3, 20 T4, and 8 T stage unknown patients. Twenty-seven patients presented with macroscopic inguinal node involvement. Of the 181 patients with uninvolved nodes at presentation, 75 received a PII to a total dose of 45-50 Gy (PII group) and 106 did not receive PII (no PII group). Compared with the no PII group, patients in the PII group were younger (60% vs. 41% of patients age <68 years, p = 0.01) and had larger tumor (T3-4 = 46% vs. 27% p = 0.01). The other characteristics were well balanced between the two groups. Median follow-up was 61 months. Fourteen patients in the no PII group vs. 1 patient in the PII group developed inguinal recurrence. The 5-year cumulative rate of inguinal recurrence (CRIR) was 2% and 16% in PII and no PII group respectively (p = 0.006). In the no PII group, the 5-year CRIR was 12% and 30% for T1-T2 and T3-T4 respectively (p = 0.02). Overall survival, disease-specific survival, and disease-free survival were similar between the two groups. In the PII group, no Grade >2 toxicity of the lower extremity was observed.
PII with a dose of 45 Gy is safe and highly efficient to prevent inguinal recurrence and should be recommended for all T3-4 tumors. For early-stage tumors, PII should also be discussed, because the 5-year inguinal recurrence risk remains substantial when omitting PII (about 10%).
We compared two intensity-modulated radiotherapy techniques for left-sided breast treatment, involving lymph node irradiation including the internal mammary chain. Inverse planned arc-therapy (VMAT) ...was compared with a forward-planned multi-segment technique with a mono-isocenter (MONOISO). Ten files were planned per technique, delivering a 50-Gy dose to the breast and 46.95 Gy to nodes, within 25 fractions. Comparative endpoints were planning target volume (PTV) coverage, dose to surrounding structures, and treatment delivery time. PTV coverage, homogeneity and conformality were better for two arc VMAT plans; V95%PTV-T was 96% for VMAT vs 89.2% for MONOISO. Homogeneity index (HI)PTV-T was 0.1 and HIPTV-N was 0.1 for VMAT vs 0.6 and 0.5 for MONOISO. Treatment delivery time was reduced by a factor of two using VMAT relative to MONOISO (84 s vs 180 s). High doses to organs at risk were reduced (V30left lung = 14% using VMAT vs 24.4% with MONOISO; dose to 2% of the volume (D2%)heart = 26.1 Gy vs 32 Gy), especially to the left coronary artery (LCA) (D2%LCA = 34.4 Gy vs 40.3 Gy). However, VMAT delivered low doses to a larger volume, including contralateral organs (mean dose Dmeanright lung = 4 Gy and Dmeanright breast = 3.2 Gy). These were better protected using MONOISO plans (Dmeanright lung = 0.8 Gy and Dmeanright breast = 0.4 Gy). VMAT improved PTV coverage and dose homogeneity, but clinical benefits remain unclear. Decreased dose exposure to the LCA may be clinically relevant. VMAT could be used for complex treatments that are difficult with conventional techniques. Patient age should be considered because of uncertainties concerning secondary malignancies.
EGFR is frequently overexpressed in cervical cancer, suggesting EGFR blockade as a promising treatment approach. Cetuximab, an anti EGFR antibody, used conjointly with radiochemotherapy, was feasible ...in first-line treatment of cervix carcinoma limited to the pelvis.
This randomized phase II trial enrolled 78 FIGO stage IB2-IIIB cervical cancer patients to either cisplatin-based radiochemotherapy alone (arm B, n = 38) or conjointly with a 6-week course of weekly cetuximab (arm A, n = 40). Brachytherapy was given to the pelvic mass. Primary endpoint was disease-free survival (DFS) at 2 years. EGFR expression and targeted sequencing were performed in 54 of 78 patients.
Cetuximab over a 6-week period did not improve DFS at 24 months. At 31 months median follow-up, DFS was not significantly different (P = 0.18). Complete response at 4 to 6 months was strongly predictive for excellent DFS (log-rank test; P < 0.001). PIK3CA, KRAS, and STK11 mutations were observed in 22%, 4%, and 2% of patients, respectively. No tumor with a PI3K pathway mutation showed complete response (0/8 in arm A and 0/6 in arm B), whereas 14 of 52 (27%) tumors without mutations did (P = 0.021). PI3K pathway-mutated tumors showed a trend toward poorer DFS (P = 0.06) following cetuximab (8/22) as compared with those following standard treatment only (6/18).
Similar to patients with head and neck cancer, patients with cervical cancer showed no gain in DFS at 2 years following a combined treatment of cetuximab with radiochemotherapy. Although treatment tolerance and compliance were satisfactory, it remains to be demonstrated whether maintenance therapy with cetuximab could be beneficial in selected patient groups.
Background: To analyze the outcomes of patients with brain metastases (BM) from non-small cell lung cancer (NSCLC) treated with immunotherapy (IT) and stereotactic radiotherapy (SRT) and to study the ...impact of the sequence between the two modalities. Methods: The authors reviewed the records of 51 patients with 84 BM from NSCLC treated at Institut Curie with IT and SRT. BM were categorized into three groups: ‘SRT before IT’, ‘concurrent SRT and IT’, and ‘SRT after IT.’ Regional progression-free interval (R-PFI) and overall survival (OS) were estimated using the Kaplan–Meier method. Results: After a median follow-up from SRT of 22.5 months (2.7–47.3), the 1-year and 2-year OS were 69.7% (95%CI 58.0–83.8) and 44.0% 30.6–63.2, respectively. Concerning distant intracranial control, the 1-year and 2-year R-PFI were 40.1% 30.1–53.3 and 35.2% 25.1–49.4, respectively. Moreover, one-year R-PFI in ‘SRT before IT’, ‘concurrent SRT and IT’, and ‘SRT after IT’ groups were 24.1%, 49.6%, and 34.2%, respectively (p = 0.094). The type of therapeutic sequence did not appear to impact the risk of brain necrosis. Conclusions: The concurrent administration of SRT and IT appeared to offer the best locoregional control, without increasing the risk of toxicity, compared to patients treated with SRT before or after IT.
Cancer patients have been reported to be at higher risk of COVID-19 complications and deaths. We report the characteristics and outcome of patients diagnosed with COVID-19 during breast cancer ...treatment at Institut Curie hospitals (ICH, Paris area, France).
An IRB-approved prospective registry was set up at ICH on March 13, 2020, for all breast cancer patients with COVID-19 symptoms or radiologic signs. Registered data included patient history, tumor characteristics and treatments, COVID-19 symptoms, radiological features, and outcome. Data extraction was done on April 25, 2020. COVID-19 patients were defined as those with either a positive RNA test or typical, newly appeared lung CT scan abnormalities.
Among 15,600 patients actively treated for early or metastatic breast cancer during the last 4 months at ICH, 76 patients with suspected COVID-19 infection were included in the registry and followed. Fifty-nine of these patients were diagnosed with COVID-19 based on viral RNA testing (N = 41) or typical radiologic signs: 37/59 (63%) COVID-19 patients were treated for metastatic breast cancer, and 13/59 (22%) of them were taking corticosteroids daily. Common clinical features mostly consisted of fever and/or cough, while ground-glass opacities were the most common radiologic sign at diagnosis. We found no association between prior radiation therapy fields or extent of radiation therapy sequelae and extent of COVID-19 lung lesions. Twenty-eight of these 59 patients (47%) were hospitalized, and 6 (10%) were transferred to an intensive care unit. At the time of analysis, 45/59 (76%) patients were recovering or had been cured, 10/59 (17%) were still followed, and 4/59 (7%) had died from COVID-19. All 4 patients who died had significant non-cancer comorbidities. In univariate analysis, hypertension and age (> 70) were the two factors associated with a higher risk of intensive care unit admission and/or death.
This prospective registry analysis suggests that the COVID-19 mortality rate in breast cancer patients depends more on comorbidities than prior radiation therapy or current anti-cancer treatment. Special attention must be paid to comorbidities when estimating the risk of severe COVID-19 in breast cancer patients.
This study aimed to assess the risk of acute and late radiation-induced toxicity in patients with COVID-19.
All the patients irradiated in Institut Curie from March to July 2020 were included if the ...first symptoms related to COVID-19 occurred no more than two months before the start of radiation therapy (RT) or 15 days after the end of RT.
Twenty-nine patients were included in this analysis. Twenty-five patients had no co-morbidities (86.2%), including morbid obesity. The diagnosis of COVID-19 infection was based on a positive SARS-CoV-2 RNA test for 18 patients (62.1%), a positive serology test for three patients (10.3%), and/or radiologic findings for 12 patients (41.4%). Three patients with symptoms highly suggestive of COVID-19 were included, although they had negative biologic tests and did not have a chest CT scan. Median time from the diagnosis of COVID-19 to the onset of RT was 5.5 days. Modification of RT course due to COVID-19 status was observed in 15 patients, including four for whom RT was definitively stopped. Six patients needed hospitalization for hypoxemic lung disease requiring intensive care. The majority of patients did not experience severe (> grade 2) acute toxicity. After a median follow-up of 6 months (IQR, 1-9 months), none of the patients had unusual clinical or radiological late toxicities.
The observed acute and late toxicities were ultimately similar to those observed in a population not infected with COVID-19. These results do not prompt modification of standard RT protocols for irradiation of COVID-19 patients.
Since the development of new radiotherapy techniques that have improved healthy tissue sparing, reirradiation (reRT) has become possible. The selection of patients eligible for reRT is complex given ...that it can induce severe or even fatal side effects. The first step should therefore be to assess, in the context of multidisciplinary staff meeting, the patient's physical status, the presence of sequelae resulting from the first irradiation and the best treatment option available. ReRT can be performed either curatively or palliatively to treat a cancer-related symptom that is detrimental to the patient’s quality of life. The selected techniques for reRT should provide the best protection of healthy tissue. The construction of target volumes and the evaluation of constraints regarding the doses that can be used in this context have not yet been fully codified. These points raised in the literature suggest that randomized studies should be undertaken to answer pending questions.
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•Innovative radiotherapy techniques are placing reirradiation back in the forefront.•Patient selection is complex and must be discussed at multidisciplinary meetings.•The prevention of radiation-induced injuries remains the priority.
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