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Management of brain metastases (BM) from small-cell lung cancer (SCLC) is complex and not supported by a strong evidence from prospective clinical trials. Owing to the different clinical and pathological characteristics of SCLC, patients with this histology were not included in the prospective studies on the value of whole-brain radiotherapy (WBRT) and local surgical or ablative radiation treatment like stereotactic radiosurgery (SRS). Chemotherapy also represents a major part of the armamentarium against BM from SCLC due to the well-recognized chemoresponsiveness of this cancer and the frequent presentation of BM with extracranial progression. WBRT in combination with chemotherapy has long been a standard approach in this setting. However, data on the neurocognitive toxicity and the lack of documented impact on overall survival of WBRT in the management of BM from other solid tumors, as well as the increasing availability of the stereotactic radiotherapy technologies, has led to the increasing use of SRS with omission of WBRT also in SCLC. In the current review the use of different modalities of radiotherapy and ways of combining radiotherapy with chemotherapy for BM from SCLC will be presented for distinct clinical situations: presentation of BM synchronous with primary, metachronous presentation of BM-without previous prophylactic cranial irradiation (PCI) vs . after PCI, and asymptomatic BM found at the staging before PCI., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd.2019.10.51). The series “Radiotherapy for Brain Metastases from Lung Cancer” was commissioned by the editorial office without any funding or sponsorship. LK served as the unpaid Guest Editor of the series and serves as an unpaid editorial board member of Journal of Thoracic Disease from Aug 2018 to Jul 2020. The other authors have no other conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

The incidence of brain metastases (BM) is estimated between 20% and 40% of patients with solid cancer. The most common cause of this failure is lung cancer, and in locally advanced non-small cell lung cancer (NSCLC) BM represent a common site of relapse in 30-55% cases. The basic criteria of therapeutic decision-making are based on the significant prognostic factors which are components of prognostic scores. The standard approach to treatment of BM from NSCLC include whole brain radiotherapy (WBRT) which is used as adjuvant modality after local therapy (surgery or stereotactic radiosurgery) or as primary treatment and it remains the primary modality of treatment for patients with multiple metastases. WBRT is also used in combination with systemic therapy. The aim of presented review of literature is trying to answer which patients with BM from NSCLC should receive WBRT and when it could be omitted. There were presented the aspects of application of WBRT in relation to (I) choice between WBRT or the best supportive care and (II) employment of WBRT in combination with local treatment modalities [surgical resection or stereotactic radio-surgery (SRS)] and/or with systemic therapy. According to data from literature we concluded that the most important factor that needs to be considered when assessing the suitability of a patient for WBRT is the patient's prognosis based on the Lung-molGPA score. WBRT should be applied in treatment of multiple BM from lung cancer in patients with favourable prognosis and in in patients with presence of EML4-ALK translocation before therapy with crizotinib. Whereas WBRT could be omitted in patients with poor prognosis and after primary SRS., Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-2019-rbmlc-06). The series “Radiotherapy for Brain Metastases from Lung Cancer” was commissioned by the editorial office without any funding or sponsorship. The authors have no conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

Objectives: Contrast-enhanced spectral mammography (CESM) is a novel method for breast cancer detection. The aim of this study is to check if there is a possibility of quantitative assessment of contrast enhancement in CESM and if there is any correlation between quantitative assessment of contrast enhancement in CESM and histopathology., Methods: A total of 167 female patients underwent CESM. All subjects previously had suspicious lesions found on mammography, breast ultrasound, or both. After imaging, the following parameters were evaluated: number of enhancing lesions in each breast and size and degree of enhancement of each lesion. Based on the collected data, the percentage signal difference between enhancing lesion and background (%RS) and signal-difference-to-noise ratio (SDNR) were measured for each lesion., Results: The number of lesions detected in the study population was 195. Among all diagnosed lesions, 120 (62%) were assessed to be infiltrating cancers, 16 (8%) non-infiltrating cancers, and 59 (30%) were benign. Thirteen (7%) lesions did not enhance in CESM; all non-enhancing lesions were confirmed to be benign under histopathological examination. Analysis of enhancement indices showed that signal values within lesions and signal values within background ROIs (regions of interest) were similar in CC (craniocaudal) and MLO (mediolateral) projections. Mean %RS values were correlated with the type of enhancing lesion, infiltrating cancers having the highest values, benign lesions the lowest., Conclusions: This work has demonstrated a significant correlation between the degree of lesion enhancement in CESM and malignancy. Quantitative analysis of enhancement levels in CESM can distinguish between invasive cancers and benign or in situ lesions., Key Points: • There is a possibility of quantitative assessment of contrast enhancement in CESM. • Correlation between quantitative assessment of contrast enhancement in CESM and histopathology was observed.

Objectives: Radiotherapy in patients with sinonasal mucosal melanoma (SNMM) was given as alternative treatment to surgery in cases with advanced, inoperable tumors or those not eligible for surgery. We presented the outcomes for patients with SNMM treated with radiotherapy alone., Material and Methods: The retrospective review of 6 consecutive SNMM (nasal cavity - 4 pts. and paranasal sinus - 2 pts.) patients (3 males and 3 females at mean age 64 years) treated between 2008 and 2016 was presented. The stage of disease was: T3 (1 pt.), T4a (3 pts.), T4b (2 pts.); with N0 and M0 in all patients. All patients underwent definitive primary photon radiotherapy (IMRT) alone; dose 66-72 Gy was delivered in 22-24 fractions given in 5 fractions (3 Gy) a week., Results: The complete remission was observed in all our patients but only one patient survived 5 years without disease. Five patients died due to multiple distant metastases; two of those patients developed associated local recurrence 7-8 months after radiotherapy., Conclusion: SNMM has a poor prognosis due to its high metastatic potential. Based on our numerically small report and data from literature we concluded that primary radiotherapy alone assured complete remission and even 5-year disease-free survival in only a few individual patients.

Gafchromic EBT3 films are applied in proton radiotherapy for 2D dose mapping because they demonstrate spatial resolution well below 1 mm. However, the film response must be corrected in order to reach the accuracy of dose measurements required for the clinical use. The in-house developed AnalyseGafchromic software allows to analyze and correct the measured response using triple channel dose calibration, statistical scan-to-scan fluctuations as well as experimentally determined dose and LET dependence. Finally, the optimized protocol for evaluation of response of Gafchromic EBT3 films was applied to determine 30 × 40 cm2 dose profiles of the scanning therapy unit at the Cyclotron Centre Bronowice, CCB in Krakow, Poland.

Background/aim: It is possible that the degree of enhancement on contrast-enhanced spectral mammography (CESM), a new diagnostic method, might provide prognostic information for breast cancer patients. Therefore, in a group of 82 breast cancer patients, we analyzed the prognostic significance of degree and pattern of enhancement on CESM as well as its relation to: (a) breast cancer immunophenotype (based on ER/PR/HER2 status) (b) podoplanin expression in cancer stroma (lymphatic vessel density plus podoplanin-positivity of cancer-associated fibroblasts), and (c) other histological parameters., Materials and Methods: For each tumor the intensity of enhancement on CESM was qualitatively assessed as strong or weak/medium, while the pattern - as homogenous and heterogenous., Results: Herein we report, for the first time, that strong and heterogenous enhancement on CESM was related to unfavorable disease-free survival of breast cancer patients (p=0.005). Moreover, the strong enhancement was more frequent in large and node-positive tumors (pT>1, pN>0) (p=0.002), as well as in carcinomas with podoplanin-sparse stroma (p=0.008)., Conclusion: Intensity and pattern of enhancement on CESM might provide (together with the results of other diagnostic imaging methods) not only the confirmation of presence or absence of tumor, but also prognostic information., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Mucinous breast carcinoma (MBC) carcinoma represents approximately 1-6% of all malignant breast carcinoma and is divided into pure (PMBC) and mixed (MMBC) subtypes. This study presents the comparison of clinical characteristics and treatment results in 70 patients with PMBC and 40 patients with MMBC, treated at a single institution during 25 years. Performed analyses showed that only nodal status was different in both subtypes. Patients with MMBC showed a significantly higher incidence of axillary nodal metastases in comparison to PMBC (25% versus 10%, respectively). Instead, the 10-year disease-free survival rate was significant higher in PMBC than MMBC (85.7% versus 65%, p < 0.02, test log rank). Authors own observations and data from literature proved that MMBC should be considered as subtypes of mucinous breast cancer., (© 2016 Wiley Periodicals, Inc.)

Background: The aim of the present study was to compare the diagnostic utility of HE4 with NSE, ProGRP, CYFRA 21-1, CEA, and CA 125 and evaluate their prognostic value in patients with small-cell lung cancer (SCLC)., Methods: HE4, ProGRP, NSE, CYFRA 21-1, CEA, and CA 125 assays were performed in 63 patients with smallcell lung cancer (limited disease (LD) - 41, extensive disease (ED) - 22) and in 66 individuals of the reference group., Results: Area under the ROC curves for HE4, ProGRP, NSE, CA 125, CYFRA 21-1, and CEA were 0.884, 0.923, 0.826, 0.796, 0.739, and 0.704, respectively. The tumor marker serum concentrations were associated with tumor stage (HE4, ProGRP, NSE, CYFRA 21-1, CEA), and disease progression occurred within one year (HE4, ProGRP, NSE, CYFRA 21-1). The tumor advancement, performance status, gender and tumor markers, except CEA and CA 125, were significantly associated with survival. Independent, unfavourable prognostic factors included extensive disease (HR 4.14, p < 0.0001) and NSE concentration above 35 g/l (HR 2.62, p = 0.0009)., Conclusions: Diagnostic utility of HE4 was similar to that of NSE and ProGRP. Complementary to NSE, determination of HE4 seems to be helpful in evaluation of SCLC patients' prognosis.

Introduction: Invasive lobular carcinoma (ILC) comprises 4-15% of all malignant neoplasms of the breast. The "classical variant of ILC" (C-ILC) constitutes some 60-80% of this cancer. The main cause of treatment failures is dissemination observed in 8-38% patients The disant metastases (DM) are frequently localized in: bones, gastrointestinal tract, uterus, leptomeninges, and ovaries. The aim of this study was to present the methods and results of the treatment of patients with DM from the classical variant of ILC (C-ILC) at a single institution in Poland., Materials and Methods: Between January 1983 and December 2004, 210 women with C-ILC of the breast were primarily treated surgically (mastectomy in 182 (86.7%) patients and breast conserving therapy in 28 (13.3%) patients). Then adjuvant therapy (radiotherapy, chemotherapy, and hormonotherapy) was applied according to presence of clinical indications., Results: The present study focused on a group of 41 patients with a median age of 59 that died with DM from C-ILC during the ten-year follow-up. This failure developed on average 65 months (3-186) after surgery of ILC. The most frequently DM developed: bones (39.1%), GI (small bowell, stomach, colon, rectum) - 31.8%, and reproductive organs (ovary, uterus) - 19.1%. In therapy of DM, different configuration surgery, radiotherapy, and chemo-hormonotherapy were used. The median survival after the diagnosis of DM was connected with localization of distant metastases., Conclusion: Patients with classic variant of infiltrate lobular cancer of breast should be regularly follow-up, which could permit early diagnosis of distant metastases and improve treatment results.

Contrast-enhanced spectral mammography (CESM) is one of the new diagnostic modalities implemented in clinical practice. In the case of these techniques, there are two major issues to be addressed: (1) their diagnostic usefulness, and (2) the relation between parameters assessed using these techniques and well-known diagnostic/prognostic/predictive markers (histological, clinical, and molecular). Therefore, we studied the relationship between the tumour margin assessed on CESM and (1) tumour borders defined on the basis of macroscopic and microscopic examination, (2) pT, (3) pN, and (4) tumour grade in a group of 82 breast cancer patients. Based on CESM, the tumour border was defined as sharp, indistinct or spiculated, whereas in the case of lesions showing weak or medium enhancement on CESM the borders were classified as unspecified. We found a statistically significant relationship between tumour margin on CESM and (1) macroscopic border (a spiculated margin on CESM was found only in carcinomas with an invasive border on histological examination; p = 0.004), (2) pT (p = 0.016), and (3) pN (nodal involvement was observed most frequently in carcinomas with a spiculated or indistinct margin on CESM; p = 0.045). Moreover, in cases with an undefined margin on CESM (cases showing weak or medium enhancement on CESM), both invasive and pushing borders were found on histological examination. The results of our preliminary study suggest that it is possible to assess macroscopic borders of examined lesions on the basis of CESM imaging. This might be useful in planning the extent of surgical excision. On the other hand, the assessment of the tumour margin on CESM might not be precise in cases showing weak enhancement.

We present the androgen receptor (AR) status in 32 breast cancers diagnosed in male patients. Androgen receptor expression was found in 62.5% tumors and it was more frequent (85% of cases) in estrogen-positive tumours. The analyses of its impact on treatment results showed that AR immmunopositivity is a prognostic factor for overall survival, and AR immunonegativity is also correlated with worse prognosis (distant metastases developed more frequently and earlier).

Background: It is assumed that lymphatic vessels are responsible for breast cancer dissemination., Patients and Methods: In 32 male breast carcinomas we evaluated the correlation between: (i) lymphatic vessel density (LVD), distribution of podoplanin-immunostained vessels (DPV), blood vessel density (BVD), infiltration of immune cells and (ii) known clinicopathological parameters., Results: Lymphatic and blood vessels were found in 77.8% and 100% of breast carcinomas, respectively. Double-negative estrogen and progesterone receptor tumors (ER-/PR-) presented significantly higher LVD than ER/PR positive cases, while high-grade tumors exhibited significantly higher DPV than low-grade carcinomas. We detected significantly higher frequency of vascular invasion in high-grade and double-negative carcinomas than in low-grade and ER/PR-positive ones, respectively., Conclusion: The relationship between high number of lymphatic vessels and high tumor grade or steroid receptor negativity might confirm the hypothesis regarding the influence of lymphangiogenesis on the formation of a more aggressive phenotype in male breast cancer., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Male breast cancer is a rare form of carcinoma with an incidence rate of approximately 0.5-1% compared with cases of breast carcinoma as a whole. Male breast cancer reacts effectively to endocrine therapy because of a high frequency of hormone receptor expression.The aim of the present study was the assessment of correlations between stage, grade, expression of steroid receptors, basal/mesenchymal markers and proliferation index, as well as analysis of the impact of the above-mentioned parameters on overall (OS) and disease-free survival (DFS) in the group of 32 male breast cancer patients, treated at the Centre of Oncology in Cracow.We showed the significant positive correlation between MIB-1 LI and tumor stage, and hormone receptors (ER or PgR) immunonegativity, and expression of EGFR, vimentin (p<0.05) and P-cadherin (the last at statistical border). The presence of any of basal or masenchymal markers correlated with a more advanced tumor stage. Moreover tumors without vimentin expression were characterised by lower MIB-1 LI and were more frequently EGFR immunonegative.We found that hormone receptor negativity, vimentin immunopositivity and high MIB-1 LI are significant independent indicators of poor OS and DFS for male breast cancer patients (p<0.05).

Purpose: The evaluation of effect of therapeutic parameters such as time of starting thoracic radiotherapy in relation to chemotherapy, schedule of combination chemo- and radiotherapy and SER, on treatment results in patients with limited disease small cell lung cancer (LD SCLC)., Methods: Between 2000 and 2007, 212 patients with LD SCLC received combined therapy: chemotherapy and thoracic radiotherapy. All patients received chemotherapy according to PE schedule (4-6 cycles), in combination with thoracic radiotherapy. The total dose applied to GTV was 54 Gy given in 27-30 fractions using fraction dose of 1.8-2.0 Gy. The concurrent treatment was performed in 112 patients (52.8%): the conventional fractionation (once a day, every five days a week) in 35 patients while 77 patients received "moderate" accelerated fractionation (one fraction a day, every four days a week and two fractions within one day, a week apart, with 6h gap). The remaining 100 patients (47.2%) received sequential treatment. The time from the first day of chemotherapy to the end of thoracic radiotherapy (SER) was evaluated in all patients. The SER ranged from 57 to 337 days with the median value of 121 days., Results: The complete response in the thorax was observed in 143 out of 212 patients (67.5%). Out of these, 82 patients received concurrent chemo-radiotherapy (given in 22 patients as conventional dose fractionation and in 60 patients according to "moderate" accelerated dose fractionation), and the remaining 61 patients were treated with sequential therapy. The 5-year survival rates were: 17.7% for overall survival (OS), and 19.3% for disease-free survival (DFS). The relationship of therapeutic factors to survival rates showed statistically significant improvement of survival ratios in relation to early starting of thoracic radiotherapy and application of concurrent chemo-radiotherapy. The results of logistic regression revealed significant relationship between the value of SER and OS and DFS. The analysis shows that each day of extension of the SER resulted in increased probability of death (decrease of OS) by 0.28% and in increased the risk of development failure (decrease of DFS) by 0.31%. The influence of SER on lowered probability of complete response frequency was not statistically significant., Conclusions: The concurrent chemo-radiotherapy with early administration of thoracic radiotherapy, results in improved complete response in the thorax and increase of overall and disease-free survival rates. The 5-year survival rates were: 17.7% for overall survival and 19.3% for disease-free survival. Our analysis and data from the literature suggest that shorter SER may play prognostic role in patients with LD SCLC treated with combination chemo- and radiotherapy. However, these observations require the confirmation in following studies., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The aim of this paper is to present results of analysis of 102 females with laryngeal cancer., Materials and Methods: Between 1974 and 1995, 102 female patients with cancer of larynx were treated at Radiotherapy Department of Oncology Centre in Kraków. Twenty-six of them had positive familial oncological history. The treatment method depended on stage of disease. Primary radical irradiation was performed in 66 patients, 29 patients received postoperative radiotherapy after surgery (total or partial laryngectomy), seven patients received induction chemotherapy followed by laryngectomy with postoperative radiotherapy or radical irradiation. The median dose applied with radiotherapy was 60 Gy, and dose per fraction was 2 Gy., Results: The actuarial 5-year rates were as follows: 88.9% for overall survival, 84.2% for disease-free survival, and 85.4% for local control. Only tumour stage and nodal involvement were found to be significant factor for all three endpoints. We found that younger patients had more supraglottic primary localisation, and these patients frequently were non-smoker., Conclusions: The tumour stage and nodal involvement were found to be significant prognostic factors in analysed group of female treated with laryngeal cancer.

Aim: To present our experience regarding the efficiency and tolerance of half-body irradiation in patients with multiple cancer metastases., Patients and Methods: Between January 1986 and December 1997, 102 patients with multiple cancer metastases received half-body irradiation (HBI) at the Center of Oncology--Maria Sklodowska-Curie Memorial Institute in Krakow. Most of the patients (93/102) had bone metastases (Table 1). The HBI was performed with 9 MV photon beam from linear accelerator. In 88 patients only one region (upper, mid or lower) was treated, and 14 patients received upper and lower HBI (13 patients), or upper and mid HBI (one patient) (Table 2). The mean doses were: 6 Gy in upper HBI, 8 Gy in mid HBI, and 9 Gy in lower HBI (Table 3)., Results: The positive palliative effect (complete or partial pain relief) was observed in 77 (75.5%) patients (Table 4). Complete pain relief was higher in patients with prostate cancer, and in patients who received mid or lower HBI. During follow-up 47 (46.1%) patients developed pain progression after treatment (Table 5). The probability of survival without pain progression was higher in patients who developed complete pain relief (86.7% at 6 months, 69.3% at 12 and 24 months) than in patients with partial response (52.9% at 6 months, 32.8% at 12 months, and 5.5% at 24 months) (Figure 1). In most of the patients (74/102, 72.5%) the tolerance was good., Conclusions: HBI is an efficient method for palliation in patients with multiple painful metastases.