Hypofractionated radiotherapy in breast cancer: a 10-year single institution experience

BackgroundModerately post-operative hypofractionated radiotherapy (HYPO-RT) for breast cancer is a safe and effective strategy as seen in large prospective trials. This study aimed to assess overall and disease-free survivals, local control, and acute and late toxicities in patients treated with HYPO-RT.Materials and methodsData from patients submitted to post-operative HYPO-RT, with or without boost, were evaluated retrospectively. Demographic, disease, and treatment characteristics were collected.ResultsFrom March 2009 to December 2016, 393 patients were treated. Breast-conserving surgery was performed in 94.7%, immediate reconstruction after mastectomy in 6 (1.5%). Most patients (91.2%) had initial stage (0 to IIA), and chemotherapy was performed in 42.0%, HYPO-RT was mainly performed in 15 or 16 daily fractions of 267 cGy and 265 cGy, respectively. The median follow-up was 5.7 years. There were 25 deaths (6.4%) and 17 (4.3%) local recurrences. At 5 and 10 years, the overall survival, local control, and disease-free survival were, respectively, 96.0% and 79.3%, 99.2% and 94.9%, 96.6%, and 91.9%. Acute grade 3 or 4 dermatitis was observed in 0.9%. Late grade 1 or 2 occurred in less than 3% of the patients.ConclusionHYPO-RT is a safe and effective radiotherapy regimen with excellent disease control and overall survival rates, with low acute and late toxicity rates.     

Short term clinical outcomes of accelerated hypofractionated radiotherapy in inoperable non-small cell lung cancer patients

BackgroundThis study aimed to evaluate short term clinical outcomes of accelerated hypofractionated radiotherapy (AHR T) regarding locoregional response (LRR), symptoms relief and acute toxicities in non-small cell lung cancer (NSCLC) patients. The radical treatment for inoperable NSCLC is intolerable for some patients. An alternative RT regime should be considered for them.Materials and methodsInoperable NSCLC patients who could not tolerate radical treatment were treated with AHRT (45 Gy in 15 fractions over three weeks) by using the 3-dimensional conformal (RT) technique. The LRR was assessed by chest computed tomography (CT) performed before and 6 weeks after RT. Relief of symptoms such as cough, dyspnoea and chest pain was evaluated during RT and 6 and 12 weeks after RT, compared with the status before RT. Treatment-related acute toxicities such as dysphagia and radiation dermatitis were observed during and 6 and 12 weeks after RT.ResultsTotal 65 patients (seven patients of stage II and fifty-eight patients of stage III) were included. Partial response was seen in 70.8% of patients, and stable disease was seen in 29.2% while there was neither complete response nor progressive disease after RT. Statistically significant associations were found between tumour response vs. pre-treatment tumour size and tumour response vs. performance status of the patients. Satisfactory symptom relief was found after RT, but severe acute dysphagia and radiation dermatitis (more than grade 3) were not observed.ConclusionSatisfactory LRR, symptom relief and acute toxicities were achieved by this regime. Long term studies are recommended to evaluate late toxicities and survival outcome further.Trial registration noTCTR20200110001     

A comparison of a moderately hypofractionated IMRT planning technique used in a randomised UK external beam radiotherapy trial with an in-house technique for localised prostate cancer

AimTo compare the radiotherapy technique used in a randomised trial with VMAT and an in-house technique for prostate cancer.BackgroundTechniques are evolving with volumetric modulated arc therapy (VMAT) commonly used. The CHHiP trial used a 3 PTV forward planned IMRT technique (FP_CH). Our centre has adopted a simpler two PTV technique with locally calculated margins.Materials and methods25 patients treated with FP_CH to 60 Gy in 20 fractions were re-planned with VMAT (VMAT_CH) and a two PTV protocol (VMAT_60/52 and VMAT_60/48). Target coverage, conformity index (CI), homogeneity index (HI), monitor units (MU) and dose to the rectum, bladder, hips and penile bulb were compared.ResultsPTV coverage was high for all techniques. VMAT_CH plans had better CI than FP_CH (p ≤  0.05). VMAT_60/52/48 plans had better CI than VMAT_CH. FP_CH had better HI and fewer MU than VMAT (p ≤  0.05). More favourable rectum doses were found for VMAT _CH than FP_CH (V_48.6, V_52.8, V₅₇, p ≤  0.05) with less difference for bladder (p ≥  0.05). Comparing VMAT_CH to VMAT_60/52/48 showed little differences for the bladder and rectum but VMAT_CH had larger penile bulb doses (V_40.8, V_48.6, mean, D_2, p ≤  0.05). Femoral head doses (V_40.8) were similarly low for all techniques (p = ≥ 0.05).ConclusionVMAT produced more conformal plans with smaller rectum doses compared to FP_CH albeit worse HI and more MU. VMAT_60/52 and VMAT_60/48 plans had similar rectal and bladder doses to VMAT_CH but better CI and penile bulb doses which may reduce toxicity.     

Early closure of phase II prospective study on acute and late tolerance of hypofractionated radiotherapy in low-risk prostate cancer patients

Aim

To assess acute and late toxicity of hypofractionated radiotherapy, its efficacy and impact on quality of life in patients with low-risk prostate cancer.

Materials and methods

Since August 2006 to October 2007, 15 prostate cancer patients with favorable clinical features, aged 54–74 years (mean 67 years) entered the study. Tumor stage in the majority (73%) of patients was T2a, the mean pretreatment PSA value was 7.2 ng/ml (range 5–10.9 ng/ml). The study group was treated 3 times a week with 4 Gy per fraction to the total dose of 60 Gy within 5 weeks. 3D conformal treatment planning was used with no fiducial markers. Acute and late toxicity was evaluated using modified EORTC/RTOG/LENT scoring systems. Patients regularly filled the EORTC QLQ-PR25 questionnaires.

Results

All patients completed radiotherapy according to the plan. During radiotherapy, 26% of patients had grade 1–2 rectal symptoms. The incidence of acute urinary toxicity score was 26%, 60%, and 14% for grade 0–1, 2 and 3, respectively. One year after RT, the incidence of grade 2 GI toxicity was 27%, which was the reason for an early closure of the accrual. Grade 2 late urinary toxicity was noted in 20% of patients. The mean PSA level was 0.61 ng/ml after 24 months and 0.47 ng/ml after 36 months (range: 0.06–1.54 ng/ml).

Conclusions

Low number of patients does not allow to determine the influence of hypofractionation on unsatisfactory tolerance of this regimen. Suboptimal (from the present day''s perspective) target localization (no fiducial markers) could potentially explain higher than expected late GI reactions in our series.     

Hypofractionated radiotherapy for early breast cancer: Review of phase III studies

Breast-conserving surgery including whole breast irradiation has long been a recommended procedure for early breast cancer. However, conventionally fractionated radiotherapy requires a lengthy hospitalisation or prolonged commuting to a hospital for radiotherapy. In recent years, hypofractionated radiotherapy has increasingly been used. This method involves higher fraction doses (above 2 Gy) as compared to conventional radiotherapy, so the total dose can be delivered in fewer fractions and in a shorter overall treatment time. This review aims at presenting most important outcomes of four randomised studies comparing conventional and hypofractionated radiotherapy schemes including a total of 7000 patients. These studies have not shown apparent differences in treatment efficacy, incidence of late post-radiotherapy complications or cosmetic effects during a 5–10 year follow-up, but longer observation is warranted to fully evaluate the safety of this method. Currently, major societies consider modestly hypofractionated radiotherapy schemes as a routine management in selected groups of patients undergoing breast-conserving surgery. However, this method should be used cautiously in patients with lymph node metastases, big breasts, receiving chemotherapy or trastuzumab, or those under 50 years of age.     

Significant impact on the oncologic outcomes with intensity modulated radiotherapy and conformational radiotherapy over conventional radiotherapy in cervix cancer patients treated with radiotherapy

ObjectiveWe designed a retrospective cohort of women with cervix cancer treated by radiation therapy with an extended follow-up to evaluate if the incorporation of modern radiation techniques was a prognostic factor.Material and methodsWe studied a cohort of patients with cervix cancer FIGO stage I-IVa treated in the last fifteen years. Patients were treated with radiotherapy alone (RT) or chemoradiation alone (CRT) using conventional radiotherapy (2DRT), conformational radiotherapy (3DRT), or intensity-modulated radiotherapy (IMRT) followed by high dose rate brachytherapy. Univariate and multivariate analysis was conducted to identify significant prognostic factors (p < 0.05).Results228 patients with cervix cancer were included. The treatment groups were CRT (64.8%), and RT (34.2%), with 31.6% submitted to 2DRT and 68.4% to IMRT/3DRT. The median follow-up was 6.3 years, the OS in 5 years according to the treatment groups was 48% for CRT, and 27.8% for RT (p < 0.001). The early-stage I-IIa (p = 0.001), CRT, and IMRT/3DRT were significant factors for better overall survival (OS) in the multivariate analysis. For the cancer-specific survival (CSS), chemoradiation, age <60 years, and IMRT/3DRT were significant. Treatment with IMRT/3DRT was the only prognostic factor associated with event-free survival (EFS).ConclusionIn a long-term follow-up, chemoradiation, early-clinical stage, and age <60 years were significant factors associated with better OS and CSS at 5 and 8 years. The incorporation of new radiation techniques, such as IMRT/3DRT, over time has a significant impact on all endpoints (EFS, OS, and CSS) of this cohort. These outcomes are useful to decide about the radiation technique to achieve satisfactory oncological results outside a clinical trial.     

Comparison between intensity modulated radiotherapy (IMRT) and 3D tangential beams technique used in patients with early-stage breast cancer who received breast-conserving therapy

Background

The most often found complications in patients with breast cancer who received radiotherapy are cardiac and pulmonary function disorders and development of second malignancies.

Aim

To compare the intensity modulated radiotherapy with the 3D tangential beams technique in respect of dose distribution in target volume and critical organs they generate in patients with early-stage breast cancer who received breast-conserving therapy.

Materials and methods

A dosimetric analysis was performed to assess the three radiotherapy techniques used in each of 10 consecutive patients with early-stage breast cancer treated with breast-conserving therapy. Radiotherapy was planned with the use of all the three techniques: 3D tangential beams with electron boost, IMRT with electron boost, and intensity modulated radiotherapy with simultaneous integrated boost.

Results

The use of the IMRT techniques enables more homogenous dose distribution in target volume. The range of mean and median dose to the heart and lung was lower with the IMRT techniques in comparison to the 3D tangential beams technique. The range of mean dose to the heart amounted to 0.3–3.5 Gy for the IMRT techniques and 0.4–4.3 for the tangential beams technique. The median dose to the lung on the irradiated side amounted to 4.9–5 Gy for the IMRT techniques and 5.6 Gy for the 3D tangential beams technique.

Conclusion

The application of the IMRT techniques in radiotherapy patients with early-stage breast cancer allows to obtain more homogenous dose distribution in target volume, while permitting to reduce the dose to critical organs.     

Role of whole brain radiotherapy in the management of infratentorial metastases from lung and breast cancer

BackgroundBrain metastases (BM) occur in almost one third of patients with systemic malignancies. Only a small number of studies focus on infratentorial location and whole brain radiotherapy (WBRT) as the main non-surgical management. The aim of the study was to compare the prognosis of patients treated with WBRT among patients with supra- or infratentorial lesions.Materials and methodsAt a single center, 263 patients with either breast (BC) or lung (LC) cancer, that had developed BM and received treatment with WBRT, were analyzed during an 8-year period.ResultsA total of 152 patients with BC and 111 with LC were analyzed, median age at the time of BM was 50.7 years, systemic activity other than BM was detected in 91%. Newly diagnosed BM were supratentorial in 40%, infratentorial in 10% and 51% in both locations. Median overall survival was 13 months (95% CI: 11.1–14.8 months), without significant difference between supra- or infratentorial location. WBRT alone was administered in 79% of patients, whereas WBRT with chemtoreapy was provided for 21%.ConclusionIn patients with BM from LC or BC that were not candidates for surgical resection, palliative WBRT appears to be equally effective in those with supra- or infratentorial locations.     

Deep inspiration breath hold in post-operative radiotherapy for right breast cancer: a retrospective analysis

BackgroundThe aim of our study is to determine whether deep inspiration breath hold (DIBH) is effective for reducing exposure of the heart, left coronary artery (LAD) and both lungs in right breast radiotherapy.Materials and methodsWe have analyzed 10 consecutive patients with right-sided breast cancer (BC), simulated during free breathing (FB) and in DIBH modality. For all patients we contoured breast PTV and organs at risk (right and left lungs, heart, LAD) on both CT scans (FB and DIBH). Finally, 5 patients were treated with IMRT and 5 with VMAT techniques.ResultsAll patients were able to end the treatments in DIBH modalities regardless of the longer treatment time in comparison to FB. The maximum and mean dose to the heart are lower in the DIBH modality. The mean values of the heart mean dose were 1.76 Gy in DIBH and 2.19 Gy in FB. The mean heart maximum dose in DIBH and FB were, respectively, 9.3 Gy and 11 Gy. Likewise, the maximum dose to the LAD is lower in DIBH; 2.57 Gy versus 3.56 Gy in FB. Noteworthy, 3 patients with hepatomegaly treated with the DIBH technique showed a higher ipsilateral lung dose than FB, but a decrease of liver dose.ConclusionWe report that the use of DIBH for right-sided BC allows the dose to the heart, LAD and to the liver to be reduced in case of hepatomegaly. This technique is well tolerated by patients, when adequately trained, and could be considered effective even in right sided BC.     

Postoperative radiotherapy in prostate cancer: Analysis of prognostic factors in a series of 282 patients

Aim

To assess the outcomes of patients treated with postoperative RT in relation to the possible prognostic factors.

Background

Postoperative radiotherapy (RT) has been proved to reduce the risk of biochemical recurrence in high-risk prostate cancer patients. Baseline prostate specific antigen (PSA), pathological Gleason score (GS), positive surgical margins, nodal status and seminal vesicle invasion are independent predictors of biochemical relapse.

Materials and methods

The clinical records of 282 patients who underwent postoperative RT were retrospectively reviewed. The prognostic value of postoperative PSA, preoperative risk class, nodal status, pathological GS, margins status, and administration of hormonal therapy (HT) was analyzed.

Results

Postoperative RT was delivered with a median dose to the prostatic fossa of 66 Gy (range 50–72) in 1.8–2 Gy/fraction. Median follow-up was 23.1 months (range 6–119). Five-year actuarial biochemical disease-free survival (bDFS) and overall survival rates were 76% and 95%, respectively. Higher bDFS was found for patients with postoperative PSA <0.02 ng/ml (p = 0.03), low preoperative risk class (p = 0.01), pN0 (p = 0.003), GS 4–6 (p = 0.0006), no androgen deprivation therapy (p = 0.02), and irrespective of surgical margin status (p = 0.10). Multivariate analysis showed that postoperative PSA and Gleason score had a significant impact on bDFS (p = 0.039 and p = 0.05, respectively).

Conclusions

Postoperative RT with a dose of 66 Gy offers an acceptable toxicity and an optimal disease control after radical prostatectomy in patients with different risk features. A postoperative PSA >0.02 ng/ml could be considered as a prognostic factor and a tool to select patients at risk for progression.     

Annexin A7 is correlated with better clinical outcomes of patients with breast cancer

The clinical prognosis of breast cancer (BC) patients remains poor. Studies on BC microarrays GSE37751, GSE7390, and GSE21653 were reanalyzed to characterize the expressions of annexin A7 (ANXA7) in BC patients and the corresponding normal breast tissues and the correlation between ANXA7 expression and clinical characteristics and survivals of BC patients. Gene set enrichment analysis (GSEA) was applied to investigate the exact mechanisms as for the expression of ANXA7 and the proliferation of BC cells. The level of ANXA7 expression was significantly decreased in BC patients than that in normal controls (P < .0001). BC patients in the ANXA7 high‐expression group were associated with better clinical features such as tumor size; histopathological grading; estrogen receptors; and clinical risk groups according to St Gallen criteria, Nottingham prognostic index criteria, and Veridex signature compared with those in the ANXA7 low‐expression group. Higher expression of ANXA7 predicted better prognosis of BC patients. The result of GSEA indicated that ANXA7 might inhibit the proliferation of BC cells through biological processes involved in androgen response, heme metabolism, and oxidative phosphorylation. The messenger RNA and protein levels of ANXA7 were decreased in BC tissues compared with those in normal breast tissues. Our results proved that ANXA7 was downregulated in BC cells and that a higher expression of ANXA7 was associated with better prognosis of BC patients.     

Matrix metalloproteases and TIMPs as prognostic biomarkers in breast cancer patients treated with radiotherapy: A pilot study

Breast cancer (BC) is the most common tumour in women and one of the most important causes of cancer death worldwide. Radiation therapy (RT) is widely used for BC treatment. Some proteins have been identified as prognostic factors for BC (Ki67, p53, E‐cadherin, HER2). In the last years, it has been shown that variations in the expression of MMPs and TIMPs may contribute to the development of BC. The aim of this pilot work was to study the effects of RT on different MMPs (‐1, ‐2, ‐3, ‐7, ‐8, ‐9, ‐10, ‐12 and ‐13) and TIMPs (‐1 to ‐4), as well as their relationship with other variables related to patient characteristics and tumour biology. A group of 20 BC patients treated with RT were recruited. MMP and TIMP serum levels were analysed by immunoassay before, during and after RT. Our pilot study showed a slight increase in the levels of most MMP and TIMP with RT. However, RT produced a significantly decrease in TIMP‐1 and TIMP‐3 levels. Significant correlations were found between MMP‐3 and TIMP‐4 levels, and some of the variables studied related to patient characteristics and tumour biology. Moreover, MMP‐9 and TIMP‐3 levels could be predictive of RT toxicity. For this reason, MMP‐3, MMP‐9, TIMP‐3 and TIMP‐4 could be used as potential prognostic and predictive biomarkers for BC patients treated with RT.     

Stereotactic radiotherapy for brain metastases in patients with lung cancer; outcome and toxicity in clinical practice

BackgroundStereotactic radiotherapy (SRT) is an established modality for treating limited brain metastases (BMs). This study aimed to assess the real-life treatment outcome and associated prognostic factors for survival in a consecutive lung cancer cohort receiving SRT for BMs.Materials and methodsA retrospective review and analysis of patients with lung cancer with BMs treated with SRT in western Sweden between 2002 and 2017 were performed. Data were collected from patient charts and the radiotherapy dose planning system.ResultsOne hundred nine patients corresponding to 139 lesions were assessed; the majority were treated with single-fractionated SRT with 20 Gy. The median overall survival (OS) was 6.1 months, with a 12-month survival rate of 24%. The estimated overall disease control rate (DCR) was 84% at a median time of three months. On multivariate analysis, WHO performance status (PS) (p = 0.002) and smoking status (p = 0.005) were significant predictive factors for survival. Four percent of the patients experienced possible grade III–IV toxicity, and previously administered cranial radiation therapy was a significant independent factor (p = 0.03) associated with the risk of developing acute toxicity.ConclusionsSRT due to brain metastases from lung cancer is a well-tolerated treatment. When selecting patients suitable for treatment, PS and extracranial disease progression should be considered. Smoking cessation is probably of value even in this palliative setting. The goal of SRT for BMs is not only to improve survival but also to provide symptom relief, and future studies on SRT should assess patient-reported outcomes in addition to survival.     

Phase I dose escalation trial of stereotactic radiotherapy prior to robotic prostatectomy in high risk prostate cancer

BackgroundThe aim of the study was to investigate the safety of combining preoperative stereotactic body radiotherapy (SBRT) with robotic radical prostatectomy (RP) for high risk prostate cancer (HRCaP). Many patients with HRCaP will require adjuvant or salvage radiotherapy after RP. The addition of preoperative SBRT before RP may spare patients from subsequent prolonged courses of RT.Materials and methodsEligible patients had NCC N HRCaP and received a total of 25 Gy or 30 Gy in five daily fractions of SBRT to the prostate and seminal vesicles followed by robotic RP with pelvic lymphadenectomy 31–45 days later. The primary endpoint was prevalence of acute genitourinary (GU) and gastrointestinal (GI) toxicity. Secondary endpoints were patient-reported quality of life (QOL) and biochemical recurrence (BcR).ResultsThree patients received preoperative SBRT to 25 Gy and four received 30 Gy. Median follow-up was 18 months. Highest toxicity was grade 2 and 3 in six (85.7%) and one (14.3%) patients, respectively. All patients developed grade 2 erectile dysfunction and 4 of 7 (57%) developed grade 2 urinary incontinence (UI) within a month after surgery. One patient developed acute grade 3 UI, but there was no grade ≥ 4 toxicity. One patient experienced acute grade 2 hemorrhoidal bleeding. On QOL, acute GU complaints were common and peaked within 3 months. Bowel symptoms were mild. Two patients with pN+ experienced BcR.ConclusionsPreoperative SBRT before robotic RP in HRCaP is feasible and safe. The severity of acute GU toxicity with preoperative SBRT may be worse than RP alone, while bowel toxicity was mild.     

Hypofractionated radiotherapy in young versus older women with breast cancer: a retrospective study from India

BackgroundYoung women with breast cancer (BC) are not represented in the trials on hypofractionation. In this study we compared outcomes in young patients with BC to their older counterparts treated with hypofractionated radiotherapy (RT) in a regional cancer centre in India.Materials and methodsBetween January 1990 to December 2010, women with BC, treated with hypofractionated RT dose of 35–40 Gy/15#/3 weeks were divided into two groups, ≤ 35 years and > 35 years. Outcomes compared were locoregional recurrence rate (LRR), locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), overall survival (OS) and toxicities. LRRFS, DFS and OS were estimated using the Kaplan-Meier method.ResultsOf total 2244 patients, 359 were ≤ 35 years of age and 1885 were > 35 years. Patient and disease characteristics were comparable between the two groups, except that comorbidities were significantly higher in the > 35 years age group, more patients aged ≤ 35 years had nodal N3 disease, received chemotherapy and RT to internal mammary nodes and more patients in the > 35 years group received hormonal therapy. Median follow up was 10 years (range 1–30 years). LRR and distant metastases were comparable between the two groups. However, synchronous LRR and distant metastases were significantly higher in the ≤ 35 years group 18 (5.1%) as compared to the > 35 years group 39 (2.1%) with p = 0.018. Estimated 10-year LRRFS, DFS and OS were 92% vs. 94% (p = 0.95), 68% vs. 73%(p = 0.058) and 78% vs. 76% (p = 0.10) in ≤ 35 years and > 35 years, respectively. OS for stage 1 was comparable between the two groups. However, for stage 2 and 3 it was 77% vs. 82% (p = 0.048) and 53% vs. 62% (p = 0.045) in the ≤ 35 years and > 35 years group, respectively. Acute and late toxicity were similar in the two groups.ConclusionYoung BC patients had higher LRR and distant metastases. LRRFS, DFS and toxicities were comparable between the two groups. However, OS was poorer in young BC patients with stage 2 and 3 disease.     

Micronuclei and other nuclear anomalies in normal human buccal mucosa cells of oral cancer patients undergoing radiotherapy: a field effect

We evaluated micronuclei and other nuclear anomalies in exfoliated epithelial cells of the oral cavity on the side opposite the lesion targeted by radiotherapy and correlated them with radiation doses. Buccal smears were obtained from oral cancer patients undergoing radiotherapy with a cumulative dose of at least 1000 rad for 3 weeks and from controls matched for age, gender and habits. The exfoliated cells from the mucosa were collected using a cytobrush; smears were prepared, fixed in 80% methanol and stained using the Feulgen plus fast green method. The mean number of micronuclei and other nuclear anomalies/1000 cells was significantly greater in patients undergoing radiotherapy treatment, but the differences were not significant compared to radiation doses. It appears that radiotherapy has a potent clastogenic effect on buccal mucosal cells of oral cancer patients.     

Radiotherapy setup displacements in breast cancer patients: 3D surface imaging experience

Aim

In this study, we intend to compare two different setup procedures for female breast cancer patients.