Alterations of Sexual and Erectile Functions after Brachytherapy for Prostate Cancer Based on Patient-Reported Questionnaires.

The aim of the study was to compare the side effects of high-dose-rate brachytherapy (HDRBT) and low-dose-rate brachytherapy (LDRBT), with a particular focus on the effects on sexual functions and sexual well-being (PROMOBRA study, NCT02258087). Localized low-risk and low-intermediate-risk prostate cancer patients were treated with mono LDR (N = 123, 145 Gy dose) or mono HDR brachytherapy (N = 117, 19/21 Gy). Prior to the treatment and during follow-up (at 3, 6, 9, 12, 18, and 24 months after treatment, and then annually after two years), patients completed patient-reported outcome measurement (PROM) questionnaires EORTC QLQ-PR-25, International Index of Erectile Function (IIEF), and IIEF-5 (SHIM). We compared the patients in different group breakdowns (HDR vs. LDR, hormone naïve and hormone-receiving HDR vs. LDR, hormone naïve and hormone-receiving patients in general, and 19 Gy HDR vs. 21 Gy HDR). In the hormone-naive LDR group, erectile function, orgasm function, sexual desire, satisfaction with intercourse, and overall satisfaction functions significantly decreased compared to baseline throughout the whole follow-up period. However, there were significant decreases in function at a maximum of three time points after HDR therapy without hormone therapy. In hormone-receiving patients, the orgasm function was significantly better in the HDR group at multiple time points compared to the baseline, and sexual desire improved at four time points. According to our results, both LDRBT and HDRBT can be safely administered to patients with localized prostate cancer. In hormone-naive patients, the HDR group showed only recovering decreases in sexual functions, while the LDR group showed a lasting decline in multiple areas. Thus, HDR appears to be more advantageous to hormone-naive patients.

Dosimetric comparison of postoperative interstitial high-dose-rate brachytherapy and modern external beam radiotherapy modalities in tongue and floor of the mouth tumours in terms of doses to critical organs.

BACKGROUND: The aim of the study was to dosimetrically compare interstitial high-dose-rate (HDR) brachytherapy (BT) and modern external beam radiotherapy modalities, as volumetric modulated arc therapy (VMAT) and stereotactic radiotherapy with Cyberknife (CK) of tumours of the tongue and floor of the mouth in terms of dose to the critical organs. PATIENTS AND METHODS: In National Institute of Oncology, Budapest, between March 2013 and August 2022 twenty patients (11 male/9 female) with stage T1-3N0M0 tongue (n = 14) and floor of mouth (n = 6) tumours received postoperative radiotherapy because of close/positive surgical margin and/or lymphovascular and/or perineural invasion. High-dose-rate interstitial brachytherapy applying flexible plastic catheters with a total dose of 15 × 3 Gy was used for treatment. In addition to BT plans VMAT and stereotactic CK plans were also made in all cases, using the same fractionation scheme and dose prescription. As for the organs at risk, the doses to the mandible, the ipsilateral and the contralateral salivary glands were compared. RESULTS: The mean volume of the planning target volume (PTV) was 12.5 cm3, 26.5 cm3 and 17.5 cm3 in BT, VMAT and CK techniques, respectively, due to different safety margin protocols. The dose to the mandible was the most favourable with BT, as for the salivary glands (parotid and submandibular) the CK technique resulted in the lowest dose. The highest dose to the critical organs was observed with the VMAT technique. The mean values of D2cm3 and D0.1cm3 for the critical organs were as follows for BT, VMAT and CK plans: 47.4% and 73.9%, 92.2% and 101.8%, 68.4% and 92.3% for the mandible, 4.8% and 6.7%, 7.3% and 13.8%, 2.3% and 5.1% for the ipsilateral parotid gland, 3.5% and 4.9%, 6.8% and 10.9%, 1.5% and 3.3% for the contralateral parotid gland, 7.3% and 9.4%, 9.0% and 14.3%, 3.6% and 5.6% for the contralateral submandibular gland. CONCLUSIONS: The present results confirm that BT, despite being an invasive technique, is dosimetrically clearly beneficial in the treatment of oral cavity tumours and is a modality worth considering when applying radiotherapy, not only as definitive treatment, but also postoperatively. The use of the CK in the head and neck region requires further investigation.

Are active dwell positions always necessary in the ring/ovoids channel of the cervical applicator in the intracavitary-interstitial brachytherapy of cervical cancer?

Purpose: To compare dosimetric parameters of brachytherapy (BT) treatment plans made with or without active source positions of the ring/ovoid (R/O) applicator in locally advanced cervical cancer patients. Material and methods: Sixty patients with cervical cancer without vaginal involvement were selected for the study, who received intra-cavitary/interstitial BT. For each patient, two plans with and without active source dwell positions in R/O were created, using the same dose-volume constraints. EQD2 total doses from external beam and BT of target volumes and organs at risk (OARs) between the competing plans were compared. Results: There was no significant difference in the dose of high-risk clinical target volume (HR-CTV) and gross tumor volume (GTV) between the plans with inactive vs. active R/O. The mean D98 of intermediate-risk clinical target volume (IR-CTV) was significantly lower with inactive R/O; however, the GEC-ESTRO (EMBRACE II study) and ABS criteria were fulfilled in 96% in both plans. There was no difference in dose homogeneity, but conformity of the plans with inactive R/O was higher. Doses to all OARs were significantly lower in plans without R/O activation. While all the plans without R/O activation fulfilled the recommended dose criteria for OARs, it was less achievable with R/O activation. Conclusions: Inactivation of R/O applicator results in similar dose coverage of the target volumes with lower doses to all OARs, as activation of R/O in cervix cancer patients when HR-CTV does not extend to R/O applicator. The use of active source positions in R/O shows worse performance regarding the fulfilment of the recommended criteria for OARs.

[BRAF-MEK inhibitor therapy in melanoma]. / BRAF-MEK gátló terápiával elért eredményeink 118, metasztatikus melanómában szenvedo betegnél az Országos Onkológiai Intézetben.

We investigated the efficacy and safety of vemurafenib+cobimetinib (V+C) and dabrafenib+trametinib (D+T) based on real-life data. From 2015 and 2018 we have selected 118 BRAF-mutated metastatic melanoma patients, treated with V+C and D+T in our institute. We retrospectively analyzed the overall response rate (ORR), the progression-free survival (PFS), the overall survival (OS) and the adverse events of the therapies. The median follow-up time was 18 months (3-43) with V+C and 12 months (3-43) with D+T. The median PFS was 8 months in the V+C and 8.5 months in the D+T group. Median OS was 18 months in V+C group and 12 months with D+T. The ORR was revealed to be 82% in D+T group and 76% in V+C group. Each combination displayed a slightly different safety profile. In our retrospective analysis both BRAF-MEK inhibitor combination therapies showed favorable efficacy with a slightly different spectrum of toxicity profile.

CyberKnife versus multicatheter interstitial brachytherapy for accelerated partial breast irradiation: a dosimetrical assessment with focus on organs at risk.

Background: The purpose of the study was to dosimetrically compare multicatheter interstitial brachytherapy (MIBT) and stereotactic radiotherapy with CyberKnife (CK) for accelerated partial breast irradiation with special focus on dose to organs at risk (OARs). Materials and methods: Treatment plans of thirty-one patients treated with MIBT were selected and additional CK plans were created on the same CT images. The OARs included ipsilateral non-target and contralateral breast, ipsilateral and contralateral lung, skin, ribs, and heart for left sided cases. The fractionation was identical (4 × 6.25 Gy). Dose-volume parameters were calculated for both techniques and compared. Results: The D90 of the PTV for MIBT and CK were similar (102.4% vs. 103.6%, p = 0.0654), but in COIN the MIBT achieved lower value (0.75 vs. 0.91, p < 0.001). Regarding the V100 parameter of non-target breast CK performed slightly better than MIBT (V100: 1.1% vs. 1.6%), but for V90, V50 and V25 MIBT resulted in less dose. Every examined parameter of ipsilateral lung, skin, ribs and contralateral lung was significantly smaller for MIBT than for CK. Protection of the heart was slightly better with MIBT, but only the difference of D2cm3 was statistically significant (17.3% vs. 20.4%, p = 0.0311). There were no significant differences among the dose-volume parameters of the contralateral breast. Conclusion: The target volume can be properly irradiated by both techniques with high conformity and similar dose to the OARs. MIBT provides more advantageous plans than CK, except for dose conformity and the dosimetry of the heart and contralateral breast. More studies are needed to analyze whether these dosimetrical findings have clinical significance.

Results of sole postoperative interstitial, high-dose-rate brachytherapy of T1-2 tongue tumours.

PURPOSE: To describe the results of treating tongue cancer patients with single postoperative interstitial, high-dose-rate (HDR) brachytherapy (BT) after resection. METHODS: Between January 1998 and April 2019, 45 patients with squamous cell histology, stage T1-2N0-1M0 tongue tumours were treated by surgery followed by a single HDR BT in case of negative prognostic factors (close or positive surgical margin, lymphovascular and/or perineural invasion). The average dose was 29 Gy (range: 10-45 Gy) and rigid metal needles were used in 11 (24%) and flexible plastic catheters in 34 cases (76%). Survival parameters, toxicities and the prognostic factors influencing survival were analysed. RESULTS: During a mean follow-up of 103 months (range: 16-260 months) for surviving patients, the 10-year local and regional control (LC, RC), overall survival (OS), and disease-specific survival (DSS) probabilities were 85, 73, 34 and 63%, respectively. The incidence of local grade 1, 2 and 3 mucositis was 23, 73 and 4%, respectively. As a serious (grade 4), late side effect, soft tissue necrosis developed in 3 cases (7%). In a univariate analysis, there was a significant correlation between lymphovascular invasion and RC (p = 0.0118) as well as cervical recurrence and DSS (p < 0.0001). CONCLUSION: Sole postoperative HDR brachytherapy can be an effective method in case of negative prognostic factors in the treatment of early, resectable tongue tumours. Comparing the results of patients treated with postoperative BT to those who were managed with surgery or BT alone known from the literature, a slightly more favourable LC can be achieved with the combination therapy, demonstrating the potential compensating effect of BT on adverse prognostic factors, while the developing severe, grade 4 toxicity rate remains low.

The value of brachytherapy in the age of advanced external beam radiotherapy: a review of the literature in terms of dosimetry.

Brachytherapy (BT) has long been used for successful treatment of various tumour entities, including prostate, breast and gynaecological cancer. However, particularly due to advances in modern external beam techniques such as intensity-modulated radiotherapy (IMRT), volume modulated arc therapy (VMAT) and stereotactic body radiotherapy (SBRT), there are concerns about its future. Based on a comprehensive literature review, this article aims to summarize the role of BT in cancer treatment and highlight its particular dosimetric advantages. The authors conclude that image-guided BT supported by inverse dose planning will successfully compete with high-tech EBRT in the future and continue to serve as a valuable modality for cancer treatment.

Low socioeconomic position is a risk factor for delay to treatment and mortality of testicular cancer patients in Hungary, a prospective study.

BACKGROUND: In Hungary, the mortality rate for testicular germ cell cancer (TGCC) is 0,9/100000 which is significantly higher than the EU average. We prospectively evaluated the effect of socioeconomic position on patient delay and therapy outcomes. METHODS: Questionnaires on subjective social status (MacArthur Subjective Status Scale), objective socioeconomic position (wealth, education, and housing data), and on patient's delay were completed by newly diagnosed TGCC patients. RESULTS: Patients belonged to a relatively high socioeconomic class, a university degree was double the Hungarian average, Cancer-specific mortality in the highest social quartile was 1.56% while in the lowest social quartile 13.09% (p = 0.02). In terms of patient delay, 57.2% of deceased patients waited more than a year before seeking help, while this number for the surviving patients was 8.0% (p = 0.0000). Longer patient delay was associated with a more advanced stage in non-seminoma but not in seminoma, the correlation coefficient for non-seminoma was 0.321 (p < 0.001). For patient delay, the most important variables were the mother's and patient's education levels (r = - 0.21, p = 0.0003, and r = - 0.20, p = 0.0005), respectively. Since the patient delay was correlated with the social quartile and resulted in a more advanced stage in non-seminoma, the lower social quartile resulted in higher mortality in non-seminoma patients (p = 0.005) but not in seminoma patients (p = 0.36) where the patient delay was not associated with a more advanced stage. CONCLUSIONS: Based on our result, we conclude that to improve survival, we should promote testicular cancer awareness, especially among the most deprived populations, and their health care providers.

Early effects of different irradiation techniques used in the treatment of prostate cancer on urination / A prosztatarák kezelésében alkalmazott besugárzási technikák vizelési képességre gyakorolt korai hatása.

Összefoglaló. Bevezetés: A prosztatarák kezelésében jelentos szerepet kapnak a különbözo sugárterápiás eljárások. Ennek ellenére a vizelési képességre gyakorolt, rövid és hosszú távú mellékhatásaikat objektív vizsgálómódszerrel igen kevés tanulmányban vizsgálták. Célkituzés: Arra a kérdésre kerestük a választ, hogy hogyan változik a korai vizelési képesség a különbözo sugárterápiás eljárások során. Módszerek: A vizsgálatunkban meghatározott protokoll szerint a kezelés elott minden bevont beteggel IPSS-t (nemzetközi prosztatatünet-értékelo lap) töltettünk ki, illetve uroflow (vizeletáramlási) vizsgálatot végeztünk, suprapubicus ultrahanggal meghatározott mictiós residuum méréssel kiegészítve. A sugárkezelés befejezésétol számított 4-6 héten belül ismételten elvégeztük ezeket a vizsgálatokat, melyekbe összesen 26 beteget vontunk be. A kezelési modalitások szerint 6, kis dózisteljesítményu (low-dose rate; LDR) brachytherapiában, 5, nagy dózisteljesítményu (high-dose rate; HDR) brachytherapiában, 12, Cyberknife (CK) készüléken extrém hipofrakcionált sugárkezelésben és 3, lineáris gyorsítón (LINAC) mérsékelten hipofrakcionált sugárkezelésben részesített prosztatarákos beteget választottunk be. A kezelések hasonlósága miatt az LDR- és a HDR-csoportot együttesen brachytherapiás csoportként (BTCS), a CK- és a LINAC-csoportot teleterápiás csoportként (TTCS) vizsgáltuk. Eredmények: A BTCS betegeinél az IPSS- és az uroflow paraméterek korai romlása (IPSS irritatív panaszok: p = 0,003, IPSS obstruktív panaszok: p = 0,011, maximális áramlás: p = 0,003, átlagos áramlás: p = 0,006) szignifikánsnak bizonyult, a TTCS-ban mindösszesen az IPSS irritatív tünetekben volt kimutatható eltérés (p = 0,011). Következtetés: A sugárterápiás modalitás kiválasztása elott javasolható az uroflow és az IPSS-vizsgálat elvégzése. Eredményeink alapján azoknál a betegeknél, akiknél a kezelés elott középsúlyos vagy súlyos dysuriás vizelési panaszok állnak fenn, a brachytherapia helyett teleterápiás módszerek alkalmazását javasoljuk, amelyek kevésbé rontják a betegek korai vizeletürítési képességét. Orv Hetil. 2021; 162(33): 1328-1334. INTRODUCTION: Various radiotherapy procedures are applied in the treatment of prostate cancer. Nevertheless, their early and late side effects measured by uroflow and residual volume measurements have not been studied extensively. OBJECTIVE: We investigated by objective methods the early changes of urination ability after different radiotherapy procedures. METHODS: According to the protocol defined in our study, all patients had their IPSS (international prostate symptom score) determined, as well as their uroflow examinations and measurements of their residual urine via suprapubic ultrasound, carried out before treatment. These tests were then repeated at 4-6 weeks after the end of their radiotherapy. A total of 26 patients were included in the study. 6 patients were treated with low-dose rate (LDR) brachytherapy and 5 patients with high-dose rate (HDR) brachytherapy, 12 patients with Cyberknife (CK) using extreme hypofractionation and 3 patients with moderately hypofractionated radiotherapy with a linear accelerator (LINAC). Due to the similarity of the treatments, the LDR and HDR groups together were also studied as brachytherapy group and the CK and LINAC patients as teletherapy group. RESULTS: We found that the early deterioration of IPSS and uroflow parameters after brachytherapy were significant (IPSS irritative symptoms: p = 0.003, IPSS obstructive symptoms: p = 0.011, maximum flow: p = 0.003, mean flow: p = 0.006), while in teletherapy only the IPSS irritative symptoms worsened significantly (p = 0.011). CONCLUSION: Based on our results, we suggest to perform uroflow examination and IPSS test before selecting therapeutic modality for patients with prostate cancer. In patients with moderate or severe urinary complaints before the treatment, we recommend to use teletherapy rather than brachytherapy. Orv Hetil. 2021; 162(33): 1328-1334.

Comparative dosimetrical analysis of intensity-modulated arc therapy, CyberKnife therapy and image-guided interstitial HDR and LDR brachytherapy of low risk prostate cancer.

BACKGROUND: The objective of the study was to dosimetrically compare the intensity-modulated-arc-therapy (IMAT), Cyber-Knife therapy (CK), single fraction interstitial high-dose-rate (HDR) and low-dose-rate (LDR) brachytherapy (BT) in low-risk prostate cancer. MATERIALS AND METHODS: Treatment plans of ten patients treated with CK were selected and additional plans using IMAT, HDR and LDR BT were created on the same CT images. The prescribed dose was 2.5/70 Gy in IMAT, 8/40 Gy in CK, 21 Gy in HDR and 145 Gy in LDR BT to the prostate gland. EQD2 dose-volume parameters were calculated for each technique and compared. RESULTS: EQD2 total dose of the prostate was significantly lower with IMAT and CK than with HDR and LDR BT, D90 was 79.5 Gy, 116.4 Gy, 169.2 Gy and 157.9 Gy (p < 0.001). However, teletherapy plans were more conformal than BT, COIN was 0.84, 0.82, 0.76 and 0.76 (p < 0.001), respectively. The D2 to the rectum and bladder were lower with HDR BT than with IMAT, CK and LDR BT, it was 66.7 Gy, 68.1 Gy, 36.0 Gy and 68.0 Gy (p = 0.0427), and 68.4 Gy, 78.9 Gy, 51.4 Gy and 70.3 Gy (p = 0.0091) in IMAT, CK, HDR and LDR BT plans, while D0.1 to the urethra was lower with both IMAT and CK than with BTs: 79.9 Gy, 88.0 Gy, 132.7 Gy and 170.6 Gy (p < 0.001). D2 to the hips was higher with IMAT and CK, than with BTs: 13.4 Gy, 20.7 Gy, 0.4 Gy and 1.5 Gy (p < 0.001), while D2 to the sigmoid, bowel bag, testicles and penile bulb was higher with CK than with the other techniques. CONCLUSIONS: HDR monotherapy yields the most advantageous dosimetrical plans, except for the dose to the urethra, where IMAT seems to be the optimal modality in the radiotherapy of low-risk prostate cancer.

Multicatheter interstitial brachytherapy versus stereotactic radiotherapy with CyberKnife for accelerated partial breast irradiation: a comparative treatment planning study with respect to dosimetry of organs at risk.

BACKGROUND: The aim of the study was to dosimetrically compare multicatheter interstitial brachytherapy (MIBT) and stereotactic radiotherapy with CyberKnife (CK) for accelerated partial breast irradiation (APBI) especially concerning the dose of organs at risk (OAR-s). PATIENTS AND METHODS: Treatment plans of thirty-two MIBT and CK patients were compared. The OAR-s included ipsilateral non-target and contralateral breast, ipsilateral and contralateral lung, skin, ribs, and heart for left-sided cases. The fractionation was identical (4 x 6.25 Gy) in both treatment groups. The relative volumes (e.g. V100, V90) receiving a given relative dose (100%, 90%), and the relative doses (e.g. D0.1cm3, D1cm3) delivered to the most exposed small volumes (0.1 cm3, 1 cm3) were calculated from dose-volume histograms. All dose values were related to the prescribed dose (25 Gy). RESULTS: Regarding non-target breast CK performed slightly better than MIBT (V100: 0.7% vs. 1.6%, V50: 10.5% vs. 12.9%). The mean dose of the ipsilateral lung was the same for both techniques (4.9%), but doses irradiated to volume of 1 cm3 were lower with MIBT (36.1% vs. 45.4%). Protection of skin and rib was better with MIBT. There were no significant differences between the dose-volume parameters of the heart, but with MIBT, slightly larger volumes were irradiated by 5% dose (V5: 29.9% vs. 21.2%). Contralateral breast and lung received a somewhat higher dose with MIBT (D1cm3: 2.6% vs. 1.8% and 3.6% vs. 2.5%). CONCLUSIONS: The target volume can be properly irradiated by both techniques with similar dose distributions and high dose conformity. Regarding the dose to the non-target breast, heart, and contralateral organs the CK was superior, but the nearby organs (skin, ribs, ipsilateral lung) received less dose with MIBT. The observed dosimetric differences were small but significant in a few parameters at the examined patient number. More studies are needed to explore whether these dosimetric findings have clinical significance.

Results of postoperative interstitial brachytherapy of resectable floor of mouth tumors.

PURPOSE: The purpose of this study was to describe the results of postoperative sole interstitial brachytherapy (BT) in patients with resectable floor of mouth tumors. METHODS AND MATERIALS: Between January 1998 and December 2017, 44 patients with squamous cell histology, stage T1-3N0-1M0 floor of mouth tumor were treated by excision of the primary lesion with or without neck dissection followed by sole high-dose-rate tumor bed BT with an average dose of 22.7 Gy (10-45 Gy) using rigid metal needles (n = 14; 32%) or flexible plastic catheters (n = 30; 68%). RESULTS: During a median followup time of 122 months for surviving patients, the probability of 5- and 10-year local and regional tumor control, overall survival (OS), and disease-specific survival (DSS) was 89% and 89%, 73% and 67%, 52% and 32%, 66% and 54%, respectively. In univariate analysis, lymphovascular invasion was a negative predictor of regional tumor control (p = 0.0062), DSS (p = 0.0056), and OS (p = 0.0325), whereas cervical recurrence was associated with worse DSS (p < 0.0001) and OS (p < 0.0001). The incidence of local Grade 1, 2, and 3 mucositis was 25%, 64%, and 11%, respectively. Grade 4 side effect, that is soft tissue necrosis occurred in four cases (9%). CONCLUSIONS: Results of postoperative sole high-dose-rate BT of floor of mouth tumors are comparable with those reported with low-dose-rate BT, and this method could improve local tumor control and DSS compared with exclusive surgical treatment.

Is stereotactic CyberKnife radiotherapy or multicatheter HDR brachytherapy the better option dosimetrically for accelerated partial breast irradiation?

OBJECTIVE: To compare dosimetrically the stereotactic CyberKnife (CK) therapy and multicatheter high-dose-rate (HDR) brachytherapy (BT) for accelerated partial breast irradiation (APBI). METHODS: Treatment plans of 25 patients treated with CK were selected, and additional plans using multicatheter HDR BT were created on the same CT images. The prescribed dose was 6.25/25 Gy in both plans to the target volume (PTV). The dose-volume parameters were calculated for both techniques and compared. RESULTS: The D90 total dose of the PTV was significantly lower with CK than with HDR BT, D90 was 25.7 Gy, and 27.0 Gy (p < 0.001). However, CK plans were more conformal than BT, COIN was 0.87, and 0.81 (p = 0.0030). The V50 of the non-target breast was higher with CK than with BT: 10.5% and 3.3% (p = 0.0010), while there was no difference in the dose of the contralateral breast and contralateral lung. Dose to skin, ipsilateral lung, and ribs were higher with CK than with BT: D1 was 20.6 Gy vs. 11.5 Gy (p = 0.0018) to skin, 11.4 Gy vs. 9.6 Gy (p = 0.0272) to ipsilateral lung and 18.5 Gy vs. 12.3 Gy (p = 0.0013) to ribs, while D0.1 to heart was lower, 3.0 Gy vs. 3.2 Gy (p = 0.0476), respectively. CONCLUSIONS: Multicatheter HDR BT yields more advantageous plans than stereotactic CyberKnife treatment in accelerated partial breast irradiation, except in terms of dose conformality and the dose to the heart. There was no difference in the dose of the contralateral breast and lung.

Biological dose summation of external beam radiotherapy for the whole breast and image-guided high-dose-rate interstitial brachytherapy boost in early-stage breast cancer.

PURPOSE: To develop an alternative method for summing biologically effective doses of external beam radiotherapy (EBRT) with interstitial high-dose-rate (HDR) brachytherapy (BT) boost in breast cancer. The total doses using EBRT boost were compared with BT boost using our method. MATERIAL AND METHODS: Twenty-four EBRT plus interstitial HDR-BT plans were selected, and additional plans using EBRT boost were created. The prescribed dose was 2.67/40.05 Gy to whole breast and 4.75/14.25 Gy BT or 2.67/10.7 Gy EBRT to planning target volume (PTV) boost. EBRT and BT computed tomography (CT) were registered twice, including fitting the target volumes and using the lung, and the most exposed volume of critical organs in BT were identified on EBRT CT images. The minimal dose of these from EBRT was summed with their BT dose, and these EQD2 doses were compared using BT vs. EBRT boost. This method was compared with uniform dose conception (UDC). RESULTS: D90 of PTV boost was significantly higher with BT than with EBRT boost: 67.1 Gy vs. 56.7 Gy, p = 0.0001. There was no significant difference in the dose of non-target and contralateral breast using BT and EBRT boost. D1 to skin, lung, and D0.1 to heart were 58.6 Gy vs. 66.7 Gy (p = 0.0025), 32.6 Gy vs. 50.6 Gy (p = 0.0002), and 52.2 Gy vs. 58.1 Gy (p = 0.0009), respectively, while D0.1 to ribs was 44.3 Gy vs. 37.7 Gy (p = 0.0062). UDC overestimated D1 (lung) by 54% (p = 0.0001) and D1 (ribs) by 28% (p = 0.0003). CONCLUSIONS: Based on our biological dose summation method, the total dose of PTV in the breast is higher using BT boost than with EBRT. BT boost yields lower skin, lung, and heart doses, but higher dose to ribs. UDC overestimates lung and ribs doses.

Biological dose summation of intensity-modulated arc therapy and image-guided high-dose-rate interstitial brachytherapy in intermediate- and high-risk prostate cancer.

PURPOSE: To present an alternative method for summing biologically effective doses of intensity-modulated arc therapy (IMAT) as teletherapy (TT), with interstitial high-dose-rate (HDR) brachytherapy (BT) boost in prostate cancer. Total doses using IMAT boost was compared with BT boost using our method. MATERIAL AND METHODS: Initially, 25 IMAT TT plus interstitial HDR-BT plans were included, and additional plans using IMAT TT boost were created. The prescribed dose was 2/44 Gy to the whole pelvis, 2/60 Gy to the prostate and seminal vesicles, and 1 × 10 Gy BT or 2/18 Gy IMAT TT to the prostate. Teletherapy computed tomography (CT) was registered with ultrasound (US) of BT, and the most exposed volume of critical organs in BT were identified on these CT images. The minimal dose of these from IMAT TT was summed with their BT dose, and these EQD2 doses were compared using BT vs. IMAT TT boost. This method was compared with uniform dose conception (UDC). RESULTS: D90 of the prostate was significantly higher with BT than with IMAT TT boost: 99.3 Gy vs. 77.9 Gy, p = 0.0034. The D2 to rectum, bladder, and hips were 50.3 Gy vs. 76.8 Gy (p = 0.0117), 64.7 Gy vs. 78.3 Gy (p = 0.0117), and 41.9 Gy vs. 50.6 Gy (p = 0.0044), while D0.1 to urethra was 96.1 Gy vs. 79.3 Gy (p = 0.0180), respectively. UDC overestimated D2 (rectum) by 37% (p = 0.0117), D2 (bladder) by 5% (p = 0.0214), and underestimated D0.1 (urethra) by 1% (p = 0.0277). CONCLUSIONS: Based on our biological dose summation method, the total dose of prostate is higher using BT boost than the IMAT. BT boost yields lower rectum, bladder, and hips doses, but higher dose to urethra. UDC overestimates rectum and bladder dose and underestimates the dose to urethra.

Does inverse planning improve plan quality in interstitial high-dose-rate breast brachytherapy?

PURPOSE: To investigate the effect of input parameters for an inverse optimization algorithm, and dosimetrically evaluate and compare clinical treatment plans made by inverse and forward planning in high-dose-rate interstitial breast implants. MATERIAL AND METHODS: By using a representative breast implant, input parameters responsible for target coverage and dose homogeneity were changed step-by-step, and their optimal values were determined. Then, effects of parameters on dosimetry of normal tissue and organs at risk were investigated. The role of dwell time modulation restriction was also studied. With optimal input parameters, treatment plans of forty-two patients were re-calculated using an inverse optimization algorithm (HIPO). Then, a pair-wise comparison between forward and inverse plans was performed using dose-volume parameters. RESULTS: To find a compromise between target coverage and dose homogeneity, we recommend using weight factors in the range of 70-90 for minimum dose, and in the range of 10-30 for maximum dose. Maximum dose value of 120% with a weight factor of 5 is recommended for normal tissue. Dose constraints for organs at risk did not play an important role, and the dwell time gradient restriction had only minor effect on target dosimetry. In clinical treatment plans, at identical target coverage, the inverse planning significantly increased the dose conformality (COIN, 0.75 vs. 0.69, p < 0.0001) and improved the homogeneity (DNR, 0.35 vs. 0.39, p = 0.0027), as compared to forward planning. All dosimetric parameters for non-target breast, ipsilateral lung, ribs, and heart were significantly better with inverse planning. The most exposed small volumes for skin were less in HIPO plans, but without statistical significance. Volume irradiated by 5% was 173.5 cm3 in forward and 167.7 cm3 in inverse plans (p = 0.0247). CONCLUSIONS: By using appropriate input parameters, inverse planning can provide dosimetrically superior dose distributions over forward planning in interstitial breast implants.

Biomarkers Associated with Clinical Outcome of Advanced Melanoma Patients Treated with Ipilimumab.

Ipilimumab was the first immunotherapy approved for metastatic melanoma in decades and is currently registered as a second-line treatment. However, new immunotherapies, in combination with ipilimumab, offer even better clinical outcomes for patients compared with single-agent treatments, at the expense of improved toxicity. The aim of this study was to evaluate the feasibility of ipilimumab outside the clinical trials and to identify survival predictors for treatment benefit. Data were collected on 47 advanced melanoma patients treated with ipilimumab between 2010 and 2015 at a single center. Association of clinical characteristics (including primary tumor characteristics), serum lactate dehydrogenase (LDH), erythrocyte sedimentation rate, absolute eosinophil, lymphocyte, and neutrophil count, neutrophil/lymphocyte and eosinophil/lymphocyte ratio with toxicity and clinical outcome were assessed using univariate and multivariate analysis. Median progression-free survival at a median follow-up of 10 months was 2.7 months and median overall survival was 9.8 months. Objective response was observed in 17% of patients and the disease control rate at week 24 was 40%. The 1- and 2-year survival rates documented were 40 and 28%, respectively. Significant association between high LDH level (>1.5× upper limit of normal) and decreased overall survival was demonstrated in uni- and multivariate analysis (hazard ratio [HR]: 3.554, 95% CI: 1.225-10.306, p = 0.019). Neither biomarkers nor clinical outcome were associated with toxicity. Using baseline serum LDH to identify patients most likely to benefit from ipilimumab therapy could serve as a simple and inexpensive biomarker of clinical outcome.

Dosimetric comparison of inverse optimisation methods versus forward optimisation in HDR brachytherapy of breast, cervical and prostate cancer.

OBJECTIVE: Dosimetric comparison of HIPO (hybrid inverse planning optimisation) and IPSA (inverse planning simulated annealing) inverse and forward optimisation (FO) methods in brachytherapy (BT) of breast, cervical and prostate cancer. METHODS: At our institute 38 breast, 47 cervical and 50 prostate cancer patients treated with image-guided interstitial high-dose-rate BT were selected. Treatment plans were created using HIPO and IPSA inverse optimisation methods as well as FO. The dose-volume parameters of different treatment plans were compared with Friedman ANOVA and the LSD post-hoc test. RESULTS: IPSA creates less dose coverage to the target volume than HIPO or FO: V100 was 91.7%, 91% and 91.9% for HIPO, IPSA and FO plans (p = 0.1784) in breast BT; 90.4%, 89.2% and 91% (p = 0.0045) in cervical BT; and 97.1%, 96.2% and 97.7% (p = 0.0005) in prostate BT, respectively. HIPO results in more conformal plans: COIN was 0.72, 0.71 and 0.69 (p = 0.0306) in breast BT; 0.6, 0.47 and 0.58 (p < 0.001) in cervical BT; and 0.8, 0.7 and 0.7 (p < 0.001) in prostate BT, respectively. In breast BT, dose to the skin and lung was smaller with HIPO and FO than with IPSA. In cervical BT, dose to the rectum, sigmoid and bowel was larger using IPSA than with HIPO or FO. In prostate BT, dose to the urethra was higher and the rectal dose was smaller using FO than with inverse methods. CONCLUSION: In interstitial breast and prostate BT, HIPO results in comparable dose-volume parameters to FO, but HIPO plans are more conformal. In cervical BT, HIPO produces dosimetrically acceptable plans only when more needles are used. The dosimetric quality of IPSA plans is suboptimal and results in unnecessary larger active lengths.

Second breast-conserving surgery and interstitial brachytherapy vs. salvage mastectomy for the treatment of local recurrences: 5-year results.

PURPOSE: The purpose of this study was to report the clinical outcomes of a second breast-conserving therapy (2nd BCT) with perioperative interstitial brachytherapy (iBT) vs. those of salvage mastectomy (sMT) in the treatment of ipsilateral breast tumor recurrences (IBTRs). METHODS AND MATERIALS: Between 1999 and 2015, 195 patients with IBTR after a previous breast-conserving treatment were salvaged either with reexcision and perioperative high-dose-rate iBT (n = 39), or with sMT (n = 156). In the 2nd BCT group, a total dose of 22 Gy in five fractions of 4.4 Gy was delivered to the tumor bed with intraoperatively implanted catheters for 3 consecutive days. RESULTS: The median followup time was 59 months (1-189) in the 2nd BCT, and 56 months (3-189) in the sMT group. The mean size of IBTR was 16 mm (2-70) vs. 24 mm (2-90), respectively (p = 0.0005), but there were no other significant differences in patient- or IBTR-related parameters between the two groups. During the followup period, 4 of 39 (10.2%) and 28 of 156 (17.9%) second local recurrences (2nd LR) occurred in the 2nd BCT and the sMT group, respectively. The 5-year actuarial rate of 2nd LR was 6% vs. 18% (p = 0.22), the 5-year probability of disease-free, cancer-specific and overall survival was 69% vs. 65% (p = 0.13), 85% vs. 78% (p = 0.32), and 81% vs. 66% (p = 0.15), respectively. In the 2nd BCT group, the rate of good to excellent cosmesis was 70%. CONCLUSIONS: 2nd BCT with perioperative high-dose-rate iBT is a safe and feasible option for the management of IBTR, resulting in similar 5-year oncological outcomes and better cosmetic results compared with sMT.