What is the current role of prophylactic cranial irradiation in the treatment algorithm for small cell lung cancer?

Prophylactic cranial irradiation (PCI) is considered an important technological advance made in oncology in an effort to reduce the incidence of brain metastases (BM) and improve overall survival (OS) of patients with small cell lung cancer (SCLC). Although it is often reported that PCI improves the therapeutic potential in limited-stage (LS) SCLC, no randomised trial has ever conclusively confirmed this. Nevertheless, PCI has been considered the standard of care for LS-SCLC since the late 1990s. The data supporting the use of PCI in LS-SCLC are based on an analysis of work performed prior to the current approach to staging [brain magnetic resonance imaging (MRI), positron emission tomography (PET)/computed tomography (CT)]. The evidence for the rationale and feasibility of this approach in the modern diagnostic era should be demonstrated. The situation with extensive stage (ES) SCLC is seemingly easier because, unlike LS-SCLC, we have data from two randomised trials. Unfortunately, their results are in direct conflict with each other. Although it is generally assumed that good control of brain disease leads to better quality of life, this has never been prospectively demonstrated. In fact, PCI is associated not only with increased treatment costs and some patient discomfort, but also with non-negligible potential toxicity. For this reason, efforts have been made to preserve cognitive function by sparing the hippocampus. This concept is called hippocampal avoidance. The optimal fractionation regimen is currently less controversial than the optimal integration of PCI into the treatment algorithm. A dose of 25 Gy administered in 10 fractions should remain the standard for the eventual use of PCI in patients with SCLC. In summary, PCI is not a conditio sine qua non in any indication. Neither in patients with LS-SCLC nor in patients with ES-SCLC has a clear improvement in OS been demonstrated at follow-up using current imaging modalities.

Hormone receptor conversion in metastatic breast cancer.

Background/Objective: Hormone receptor (HR) status is one of the key factors in determining the treatment of breast cancer. Previous studies suggested that HR status may change in metastatic tissue. However, available studies focused mainly on primary biopsies and there are only few trials comparing HR status in the primary tumour and the metastasis using material from complete resection. The aim of the study was to determine the frequency of HR alterations in metastatic breast cancer. Materials and methods: The study retrospectively examines a total of 50 patients who underwent brain, lung, or liver metastasectomy for metastatic breast cancer between January 2000 and January 2019. Results: HR conversion was observed in a total of 30 cases (60.0%), while HER-2/neu (human epidermal growth factor receptor 2) discrepancy surprisingly occurred only in one case (2.0%). A change in immunophenotype occurred in 28% of cases. Triple-negativity was more frequent in brain metastases (p = 0.039). Conclusions: We have confirmed that HR conversion between the primary tumour and its metastases occurs in a significant number of cases, which has important implications for further treatment decisions.

Treatment outcomes of MRI-guided adaptive brachytherapy in patients with locally advanced cervical cancer: institutional experiences.

PURPOSE: Image-guided adaptive brachytherapy (IGABT) is currently state of the art in the comprehensive treatment of patients with cervical cancer. Here, we report mature clinical data regarding IGABT of cervical cancer in a large patient sample, examining clinical outcomes, manifestations of late toxicities, and dosimetric findings. METHODS: Between May 2012 and October 2020, we performed a total of 544 uterovaginal IGABT applications in 131 consecutive patients with biopsy-proven cervical carcinoma not suitable for surgery. The median duration of follow-up was 43 months. RESULTS: The estimated 3­, 4­, and 5­year LC rates were 88.3% (95% confidence interval [CI] 81.1-95.5), 86.9% (95% CI 78.5-95.3), and 85.5% (95% CI 76-95%), respectively. The 3­, 4­, and 5­year OS estimates were 72.66% (95% CI 63.64-81.69%), 68.9% (95% CI 59.15-78.66%), and 63.96% (95% CI 52.94-74.97%), respectively. Patients who received ≥ 5 cycles of chemotherapy had statistically significantly better 3­year recurrence-free survival (RFS) compared to patients who completed <5 cycles (79.07% [95% CI 60.81-97.34] vs. 58.10% [95% CI 47.22-68.98]; p = 0.0185). We recorded manifestations of genitourinary and gastrointestinal toxicity grade ≥3 in 6.9% and 5.3%, respectively. CONCLUSION: Our mature long-term data on the treatment patients with locally advanced cervical cancer show that excellent treatment outcomes can be achieved with MRI-based IGABT, as well as acceptable late morbidity.

Inoperable CASTLE of the thyroid gland treated with radical radiotherapy with complete remission.

Carcinoma showing thymus-like elements (CASTLE) is an extremely rare malignant tumor of the thyroid gland and soft tissues of the neck with favorable prognosis. Histological features of the CASTLE are similar to thymic carcinoma, and it is assumed that it arises from the ectopic thymic tissue or the remnants of branchial pouches. The optimal treatment strategy is still uncertain because of the rarity of the tumor. The mainstay of treatment is surgery. The role of other modalities is unclear. We present a case report of a patient with locally advanced CASTLE of the thyroid gland who was not suitable for surgery and underwent radical radiotherapy with subsequent achievement of complete remission. We also present a literature review.

Prediction of treatment response in patients with locally advanced cervical cancer using midtreatment PET/MRI during concurrent chemoradiotherapy.

PURPOSE: We aimed to find metabolic, functional or morphological characteristics of the tumor predicting failure to achieve complete metabolic remission (CMR) by the midtreatment PET/MRI (positron emission tomography/magnetic resonance imaging) in cervical cancer patients. METHODS: We evaluated 66 patients treated between August 2015 and November 2019 who underwent pretreatment staging, subsequent midtreatment evaluation, and definitive restaging 3 months after completing the whole treatment, all using PET/MRI. The pretreatment parameters (pre-SUVmax, pre-SUVmean, pre-MTV, pre-MTV­S, pre-TLG, pre-TLG­S [SUV: standard uptake value, MTV: metabolic tumor volume, TLG: total lesion glycolysis]), and the midtreatment parameters at week 5 during chemoradiotherapy (mid-SUVmax, mid-SUVmean, mid-MTV, mid-MTV­S, mid-TLG and mid-TLG-S) were recorded. The value of ADC (apparent diffusion coefficient) was also measured. Furthermore, we recorded absolute and relative changes in all parameters-∆ and ∆%. We divided the whole group of patients into "responders" (CMR) and "non-responders" (non-CMR), and compared them on the basis of the parameters from pre-PET/MRI and mid-PET/MRI. RESULTS: A statistically significant difference in the evaluated parameters between responders and non-responders was found for the following parameters: mid-MTV, mid-TLG, mid-TLG­S, mid-MTV­S, mid-tumor size, and ∆%SUVmax. According to the ROC (receiver operating characteristic) analysis, mid-MTV­S showed the best albeit moderate discrimination ability for the prediction of non-CMR. Significant mutual correlations of all variables, in particular between mid-MTV­S and mid-TLG­S and between mid-MTV and mid-TLG, were found (all p < 0.05). CONCLUSION: Our study confirmed that when using the midtreatment PET/MRI we are able to identify metabolic parameters having the discrimination ability for the prediction of non-CMR. In particular mid-MTV­S, mid-MTV, mid-tumor size, mid-TLG­S, mid-TLG and ∆%SUVmax.

Cardiac toxicity of lung cancer radiotherapy.

Radical radiotherapy of lung cancer with dose escalation has been associated with increased tumor control. However, these attempts to continually improve local control through dose escalation, have met mixed results culminating in the findings of the RTOG trial 0617, where the heart dose was associated with a worse overall survival, indicating a significant contribution to radiation-induced cardiac morbidity. It is, therefore, very likely that poorly understood cardiac toxicity may have offset any potential improvement in overall survival derived from dose escalation and may be an obstacle that limits disease control and survival of patients. The manifestations of cardiac toxicity are relatively common after high dose radiotherapy of advanced lung cancers and are independently associated with both heart dose and baseline cardiac risk. Toxicity following the treatment may occur earlier than previously thought and, therefore, heart doses should be minimized. In patients with lung cancer, who not only receive substantial heart dose, but are also older with more comorbidities, all cardiac events have the potential to be clinically significant and life-threatening. Sophisticated radiation treatment planning techniques, charged particle therapy, and modern imaging methods in radiotherapy planning, may lead to reduction of the heart dose, which could potentially improve the clinical outcomes in patients with lung cancer. Efforts should be made to minimize heart radiation exposure whenever possible even at doses lower than those generally recommended. Heart doses should be limited as much as possible. A heart dosimetry as a whole is important for patient outcomes, rather than emphasizing just one parameter.

Stewart-Treves syndrome: Case report and literature review.

Lymphangiosarcoma, or Stewart-Treves Syndrome (STS), is a very rare skin angiosarcoma with poor prognosis, which usually affects the upper limbs of patients who underwent breast cancer surgery, including axillary dissection followed by radiotherapy (RT). Cutaneous lymphangiosarcomas, which account for approximately 5% of all angiosarcomas, usually originate in the limb with chronic lymphedema. Lymphatic blockade is involved in the onset of STS. RT contributes indirectly to an increased risk of developing STS by causing axillary-node sclerosis and resulting in a lymphatic blockade and lymphedema. Chronic lymphedema causes local immunodeficiency, which indirectly leads to oncogenesis. Currently, axillary nodes are no longer routinely irradiated after axillary dissection, which is associated with a reduction in the incidence of chronic lymphedema from 40% to 4%. The use of sentinel lymph node biopsy technique is also widespread and the associated risk of lymphedema is further reduced. Thus, the incidence of STS decreased significantly with improved surgical and radiation techniques. The overall prognosis of STS patients is very poor. Only early radical surgical removal, including amputation or disarticulation of the affected limb, or wide excision at an early stage offers the greatest chance of long-term survival. Only a few case reports and series with a small number of patients with lymphangiosarcoma can be found in the literature. We present a case report of the first diagnosed STS at our department in an effort to highlight the need of the consideration of developing lymphangiosarcoma in patients with chronic lymphedema.

Late side effects of 3T MRI-guided 3D high-dose rate brachytherapy of cervical cancer : Institutional experiences.

PURPOSE: This article reports experiences with 3T magnetic resonance imaging(MRI)-guided brachytherapy (BT) for cervical cancer focusing on late side effects. METHODS: Between June 2012 and March 2017 a total of 257 uterovaginal BT administrations were performed in 61 consecutive patients with inoperable cervical cancer. All patients were treated with BT combined with external beam radiotherapy. RESULTS: The mean HR-CTV (high risk-clinical target volume) D90 was 87 ± 5.1 Gy equivalent dose corresponding to the conventional fractionation using 2 Gy per fraction (EQD2, range 70.7-97.9 Gy). The mean doses in OAR (organs at risk), namely rectum, sigmoid and bladder were D2 cm3rectum = 62.6 ± 6.9 Gy EQD2 (range 38.2-77.2 Gy), D2 cm3sigmoid = 66.2 ± 6.8 Gy EQD2 (43.2-78.6 Gy) and D2 cm3bladder = 75.1 ± 8.3 Gy EQD2 (58.2-92.6 Gy). There were no signs of late gastrointestinal (GI) toxicity in 49 patients, grade 3 toxicity was seen in 2 patients and grade 4 toxicity in 3 patients. There were no signs of late genitourinary (GU) toxicity in 41 patients, grade 3 toxicity was seen in 4 patients and no signs of grade 4 toxicity were seen. After the treatment, 60 patients (98.4%) achieved locoregional remission. In 54 patients (88.5%) the remission was complete, whereas in 6 patients (9.8%) remission was partial. CONCLUSION: The use of 3T MRI-guided BT leads to achievement of high rates of local control with limited late morbidity as demonstrated in this series of patients.

Neoadjuvant chemoradiotherapy of the rectal carcinoma - The correlation between the findings on the restaging multiparametric 3T MRI scanning and the surgical findings.

AIM: To figure out how to correlate the findings on functional MRI and carried out after neoadjuvant CRT of rectal carcinoma with final histology after surgery. BACKGROUND: Neoadjuvant CRT is the standard treatment of locally advanced rectal carcinoma. Its use leads to the downstaging of the disease and in 15-42% of patients even to the detection of pCR after TME. The use of functional MRI improves the sensitivity and specificity of pCR detection up to 52-64% and 89-98%, respectively. MATERIALS AND METHODS: Between January 2013 and June 2016, 67 patients suffering from histologically proven locally advanced rectal cancer underwent neoadjuvant RT or CRT. We selected for further investigation only patients (33 patients) who underwent pelvic staging and restaging using multiparametric imaging on 3T MRI scanner. We compared the findings on functional MRI after neoadjuvant CRT with final histology after surgery. RESULTS: In 15 patients pathologic staging of primary tumor differed from expected staging assessed according to preoperative MRI. In 5 patients pathologic complete remission was achieved. In none of these 5 patients pCR was predicted using preoperative MRI. Sensitivity and specificity of MRI in predicting pCR were 0% and 96%. Accuracy of MRI in predicting pT and pN was 79% and 74%. CONCLUSIONS: We have verified that the use of neoadjuvant CRT in the treatment of locally advanced rectal carcinoma leads to a possible achievement of pCR. But in our group of patients this was not predictable nor was it with the use of multiparametric 3T MRI.

Effectiveness of PET/CT with (18)F-fluorothymidine in the staging of patients with squamous cell head and neck carcinomas before radiotherapy.

AIM: The aim of our study was to compare the staging of the disease declared before anticancer treatment was begun with the staging that was found after the planning PET/CT scanning with (18)F-FLT was performed. BACKGROUND: PET/CT in radiotherapy planning of head and neck cancers can facilitate the contouring of the primary tumour and the definition of metastatic lymph nodes. MATERIALS AND METHODS: Between November 2010 and November 2013, 26 patients suffering from head and neck carcinomas underwent planning PET/CT examination with (18)F-FLT. We compared the staging of the disease and the treatment strategy declared before and after (18)F-FLT-PET/CT was performed. RESULTS: The findings from (18)FLT-PET/CT led in 22 patients to a change of staging: in 19 patients it led to upstaging of the disease and in 3 patients it led to downstaging of the disease. In one patient, a secondary malignancy was found. CONCLUSIONS: We have confirmed in this study that the use of (18)F-FLT-PET/CT scanning in radiotherapy planning of squamous cell head and neck carcinomas has a great potential in the precise evaluation of disease staging and consequently in the precise determination of target volumes.

The impact of PET/CT scanning on the size of target volumes, radiation exposure of organs at risk, TCP and NTCP, in the radiotherapy planning of non-small cell lung cancer.

AIM: To compare radiotherapy plans made according to CT and PET/CT and to investigate the impact of changes in target volumes on tumour control probability (TCP), normal tissue complication probability (NTCP) and the impact of PET/CT on the staging and treatment strategy. BACKGROUND: Contemporary studies have proven that PET/CT attains higher sensitivity and specificity in the diagnosis of lung cancer and also leads to higher accuracy than CT alone in the process of target volume delineation in NSCLC. MATERIALS AND METHODS: Between October 2009 and March 2012, 31 patients with locally advanced NSCLC, who had been referred to radical radiotherapy were involved in our study. They all underwent planning PET/CT examination. Then we carried out two separate delineations of target volumes and two radiotherapy plans and we compared the following parameters of those plans: staging, treatment purpose, the size of GTV and PTV and the exposure of organs at risk (OAR). TCP and NTCP were also compared. RESULTS: PET/CT information led to a significant decrease in the sizes of target volumes, which had the impact on the radiation exposure of OARs. The reduction of target volume sizes was not reflected in the significant increase of the TCP value. We found that there is a very strong direct linear relationship between all evaluated dosimetric parameters and NTCP values of all evaluated OARs. CONCLUSIONS: Our study found that the use of planning PET/CT in the radiotherapy planning of NSCLC has a crucial impact on the precise determination of target volumes, more precise staging of the disease and thus also on possible changes of treatment strategy.

Radiation-associated angiosarcoma of the breast: An international multicenter analysis.

INTRODUCTION: Radiation-associated angiosarcoma (RAAS) is a rare and serious complication of breast irradiation. Due to the rarity of the condition, clinical experience is limited and publications on this topic include only retrospective studies or case reports. MATERIALS AND METHODS: All patients diagnosed with RAAS between January 2000 and December 2017 in twelve centers across the Czech Republic and Slovakia were evaluated. RESULTS: Data of 53 patients were analyzed. The median age at diagnosis was 72 (range 44-89) years. The median latency period between irradiation and diagnosis of RAAS was 78 (range 36-172) months. The median radiation dose was 57.6 (range 34-66) Gy. The whole breast radiation therapy with radiation boost to the tumor bed was the most common radiotherapy regimen. Total mastectomy due to RAAS was performed in 43 patients (81%), radical excision in 8 (15%); 2 patients were not surgically treated due to unresectable disease. Adjuvant chemotherapy followed surgical therapy of RAAS in 18 patients, 3 patients underwent adjuvant radiotherapy. The local recurrence rate of RAAS was 43% and the median time from surgery to the onset of recurrence was 7.5 months (range 3-66 months). The 3-year survival rate was 56%, the 5-year survival rate was only 33%. 46% of patients died during the follow-up period. CONCLUSION: The present data demonstrate that RAAS is a rare condition with high local recurrence rate (43%) and mortality (the 5-year survival rate was 33%.). Early diagnosis of RAAS based on biopsy is crucial for treatment with radical intent. Surgery with negative margins constitutes the most important part of the therapy; the role of adjuvant chemotherapy and radiotherapy is still unclear.

Hypofractionated radiation therapy for breast cancer: Preferences amongst radiation oncologists in Europe - Results from an international survey.

BACKGROUND AND PURPOSE: We aimed to assess the prescription preference about hypofractionated radiation therapy (HFRT) for breast cancer (BC) patients amongst radiation oncologists (ROs) practicing in Europe and to identify restraints on HFRT utilisation. MATERIALS AND METHODS: An online survey was circulated amongst ROs in Europe through personal, RO and BC societies' networks, from October 2019 to March 2020. The statistical analyses included descriptive statistics, chi-squared testing, and logistic regression analysis. RESULTS: We received 412 responses from 44 countries. HFRT was chosen as the preferred schedule for whole breast irradiation (WBI) by 54.7% and for WBI with regional nodes irradiation (RNI) by 28.7% of the responding ROs. In the case of postmastectomy RT with or without reconstruction, HFRT was preferred by 21.1% and 29.6%, respectively. Overall, 69.2% of the responding ROs selected at least one factor influencing the decision to utilise HFRT, the most frequent of which included age (51.4%), RNI (46.9%), internal mammary lymph nodes irradiation (39.7%), BC stage (33.5%) and implant-based breast reconstruction (31.6%). ROs working in academic centres (odds ratio, (OR), 1.7; 95% confidence interval, (CI); 1.1-2.6, p = 0.019), practicing in Western Europe (OR, 4.2; 95%CI; 2.7-6.6, p < 0.0005) and/or dedicating >50% of clinical time to BC patients (OR, 2.5; 95%CI; 1.5-4.2, p = 0.001) more likely preferred HFRT. CONCLUSION: Although HFRT is recognised as a new standard, its implementation in routine RT clinical practice across Europe varies for numerous reasons. Better dissemination of evidence-based recommendations is advised to improve the level of awareness about this clinical indication.

Alopecia and Hair Damage Induced by Oncological Therapy.

Damage and loss of hair (alopecia) is a predictable adverse event of oncological therapy. It can be caused by chemotherapy, radiotherapy, or targeted and hormonal therapy. From the point of view of patients with malignant disease, hair loss is one of the most feared side effects and adversely affects their mental health. Hair loss can be diffuse, complete, partial, or regional. Worsening of hair quality, cutaneous inflammation, and scarring can also occur. Eyelashes, eyebrows, and body hair can also be lost. Alopecia is mostly reversible, but permanent damage can occur depending on the type, overall length, and dose of oncological treatment and other factors. The risk of alopecia is high with high-dose docetaxel, doxorubicin, and cyclophosphamide, but low with platinum chemotherapy, melphalan, and capecitabin. Targeted therapy and immunotherapy can cause immune-mediated alopecia such as alopecia areata and scarring alopecia as well as paradoxically hypertrichosis and trichomegaly. Physical and pharmacological approaches can be used to prevent and treat alopecia; however, their effectiveness and availability are limited. Modern radiotherapy scalp-sparing methods minimize hair loss. Good results have been obtained with scalp cooling, which reduces the toxic effects of cytostatic agents on hair follicles during short infusion regimens. Several systems cool the scalp to less than 22°C. Minoxidil accelerates hair regrowth and is used as a topical therapy. Psychological support and provision of cosmetically acceptable head coverings are also very important.

Hybrid Imaging PET/CT with Application of 18F-Fluorothymidine in Patients with Head and Neck Carcinoma Undergoing Radiotherapy.

AIM: To introduce the possible benefits of the positron-emission tomography (PET)/computed tomography (CT) with 18F-3'-deoxy-3'-fluorothymidine (18F-FLT) in patients with orofacial carcinomas and its impact to patient management. MATERIALS AND METHODS: Thirty-six patients with orofacial squamous cell carcinomas underwent 18F-FLT-PET/CT during radiotherapy. Examinations were performed after administration of 18F-FLT (1.8 MBq/kg) including full-diagnostic CT. Analysis of the radiotherapy effect was performed with possible prospect of repeated and focused irradiation. RESULTS: Complete absence of 18F-FLT uptake was found in 20 patients, thus complete response to radiotherapy was reported. Persistence of focal 18F-FLT uptake was observed in 16 patients; in 11 patients, the measured activity was only mild. In five patients, a higher level of 18F-FLT uptake was measured and additional irradiation was performed in defined regions. Repeated follow-up proved complete regression 18F-FLT uptake. CONCLUSION: It was possible to assess the effect of radiotherapy with the use of 18F-FLT-PET/CT and findings are suitable for radiation dose-escalation planning.