A current standard treatment for locally advanced prostate cancer is external-beam radiotherapy combined with 3 years of androgen suppression. Adverse events, such as myocardial infarction, are ...associated with long-term androgen suppression. This trial examined survival after treatment with long-term (3 years) or short-term (6 months) androgen suppression, plus external-beam radiotherapy, in men with locally advanced prostate cancer. Overall and prostate-cancer–specific survival in the group receiving short-term androgen suppression was inferior to that in the group receiving long-term suppression.
This trial examined survival after treatment with long-term (3 years) or short-term (6 months) androgen suppression, plus external-beam radiotherapy, in men with locally advanced prostate cancer. Overall and prostate-cancer–specific survival in the group receiving short-term androgen suppression was inferior.
Overall survival among patients with locally advanced prostate cancer has improved with the use of external-beam radiotherapy combined with long-term androgen suppression (≥2 years) as compared with the use of external-beam radiotherapy and deferral of hormonal treatment until relapse.
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However, long-term androgen suppression can reduce the quality of life and increase the risk of fatal myocardial infarction,
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fractures,
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and the metabolic syndrome.
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These risks might be lowered by replacing long-term androgen suppression with short-term suppression (6 months), which has been found to reduce mortality from localized prostate cancer.
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The European Organization for Research and Treatment of Cancer (EORTC) conducted . . .
This large population‐based study compared breast‐conserving surgery with radiation therapy (BCT) with mastectomy on (long‐term) breast cancer‐specific (BCSS) and overall survival (OS), and ...investigated the influence of several prognostic factors. Patients with primary T1‐2N0‐2M0 breast cancer, diagnosed between 1999 and 2012, were selected from the Netherlands Cancer Registry. We investigated the 1999–2005 (long‐term outcome) and the 2006–2012 cohort (contemporary adjuvant systemic therapy). Cause of death was derived from the Statistics Netherlands (CBS). Multivariable analyses, per time cohort, were performed in T1‐2N0‐2, and separately in T1‐2N0‐1 and T1‐2N2 stages. The T1‐2N0‐1 stages were further stratified for age, hormonal receptor and HER2 status, adjuvant systemic therapy and comorbidity. In total, 129,692 patients were included. In the 1999–2005 cohort, better BCSS and OS for BCT than mastectomy was seen in all subgroups, except in patients < 40 years with T1‐2N0‐1 stage. In the 2006–2012 cohort, superior BCSS and OS were found for T1‐2N0‐1, but not for T1‐2N2. Subgroup analyses for T1‐2N0‐1 showed superior BCSS and OS for BCT in patients >50 years, not treated with chemotherapy and with comorbidity. Both treatments led to similar BCSS in patients <50 years, without comorbidity and those treated with chemotherapy. Although confounding by severity and residual confounding cannot be excluded, this study showed better long‐term BCSS for BCT than mastectomy. Even with more contemporary diagnostics and therapies we identified several subgroups that may benefit from BCT. Our results support the hypothesis that BCT might be preferred in most breast cancer patients when both treatments are suitable.
What's new?
While breast‐conserving therapy (BCT) and mastectomy have long been considered equivalent in terms of survival in early‐stage breast cancer, recent studies suggest BCT offers superior survival over mastectomy. The findings of this study support that idea, showing that breast cancer‐specific survival and overall survival were greater for BCT than mastectomy in analyses of 129,692 patients diagnosed with breast cancer in The Netherlands between 1999 and 2012. Subgroup analyses revealed better survival for BCT in most instances, with survival being similar for BCT and mastectomy primarily among patients under age 50, patients without comorbidity, and those treated with chemotherapy.
Here we report for the first time the relation between breast cancer subtypes and 10‐year recurrence rates and mortality in the Netherlands. All operated women diagnosed with invasive non‐metastatic ...breast cancer in 2005 in the Netherlands were included. Patients were classified into breast cancer subtypes according to ER, PR, HER2 status and grade: luminal A, luminal B, HER2 positive and triple negative. Percentages and hazards of recurrence were compared among subtypes. Adjusted 10‐year overall (OS) and recurrence‐free survival (RFS) were calculated using multivariable Cox regression. Of 8,062 patients, 4,482 (56%) were luminal A, 2,090 (26%) luminal B, 504 (6%) HER2 positive and 986 (12%) triple negative. Local recurrences (7.5%) and distant metastases (25.6%) occurred most often in HER2 positive disease and the least often in luminal A (3.7% and 9.5%, respectively). Regional recurrences were most often diagnosed in triple negative disease (5.2%), and the least often in luminal A (1.7%). HER2 positive and triple negative subtypes had the highest recurrence rates in the second year, while luminal A and B showed a more continuous pattern over time, with lobular tumours recurring more often. After adjustment for differences in baseline characteristics, triple negative disease showed worse 10‐year OS and triple negative and HER2 positive disease had the lowest 10‐year RFS. In the Netherlands, breast cancer subtypes are important predictors for 10‐year recurrence rates. Knowledge on recurrence and survival rates according to these different subtypes, in combination with other prognostic factors, can support patient‐tailored treatment and individualised follow‐up.
What's new?
While breast cancer subtypes are known independent predictors of survival and recurrence risk, data on long‐term recurrences in daily practice remain scarce. In this population‐based study reporting on 10‐year recurrences, HER2 positive and triple negative subtypes showed the highest recurrence rates, which occurred most often in the second year, while luminal A and B recurred later on during the follow‐up. Lobular tumours recurred more often than ductal tumours. In the Netherlands, breast cancer subtypes are thus important predictors for 10‐year recurrence rates. Knowledge on recurrence and survival rates according to these different subtypes can help support patient‐tailored treatment and individualised follow‐up.
Purpose
To identify weak points in daily routine use of radiation therapy (RT) for non-metastatic breast cancer patients, particularly when data are lacking or equivocal, a “think tank” of experts ...met in Assisi.
Methods
Before the meeting, controversial issues on non-metastatic breast cancer were identified and reviewed, and clinical practice investigated by means of an online questionnaire. During the 3-day meeting, topics were discussed in-depth with attendees and potential sponsors that are involved in breast cancer treatment.
Results
Three issues were identified as needing further investigation: (1) Regional lymph node treatment in early-stage breast cancer; (2) Combined post-mastectomy RT and breast reconstruction; (3) RT in patients treated with primary systemic therapy. Future research proposals included the following: (1) Participating in appropriately selected on-going clinical trials; (2) Designing new randomized controlled clinical trials and prospective population cohort studies; (3) Setting-up large database(s) to generate predictive response models and detect biomarkers for tailored loco-regional treatments.
Conclusions
It is hoped that the ATTM findings, as described in the present white paper, will stimulate a new generation of radiation oncologists to focus on research in these areas, and that the white paper will become a tool for multidisciplinary groups to help them design research proposals and strategies.
Despite efforts to reduce the incidence of second cancer, the risk was not lower among 5-year survivors of Hodgkin's lymphoma in the Netherlands treated between 1989 and 2000, a period when more ...limited radiation fields and doses were used, than in earlier periods.
Since the late 1960s, when combination chemotherapy and high-energy radiation therapy were introduced for the treatment of Hodgkin’s lymphoma, survival has increased dramatically. Cure has come at a price, however, because the treatment of Hodgkin’s lymphoma has been shown to increase the risk of subsequent malignant neoplasms and other late effects considerably.
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Although very high relative risks have been observed for leukemia (especially among patients who were treated with alkylating agents) and non-Hodgkin’s lymphoma (which was not previously associated with a particular type of therapy), second solid cancers, the occurrence of which is related primarily to radiation therapy, contribute . . .
Up to 30% of patients who undergo radiation for intermediate- or high-risk localized prostate cancer relapse biochemically within 5 years. We assessed if biochemical disease-free survival (DFS) is ...improved by adding 6 months of androgen suppression (AS; two injections of every-3-months depot of luteinizing hormone-releasing hormone agonist) to primary radiotherapy (RT) for intermediate- or high-risk localized prostate cancer.
A total of 819 patients staged: (1) cT1b-c, with prostate-specific antigen (PSA) ≥ 10 ng/mL or Gleason ≥ 7, or (2) cT2a (International Union Against Cancer TNM 1997), with no involvement of pelvic lymph nodes and no clinical evidence of metastatic spread, with PSA ≤ 50 ng/mL, were centrally randomized 1:1 to either RT or RT plus AS started on day 1 of RT. Centers opted for one dose (70, 74, or 78 Gy). Biochemical DFS, the primary end point, was defined from entry until PSA relapse (Phoenix criteria) and clinical relapse by imaging or death of any cause. The trial had 80% power to detect hazard ratio (HR), 0.714 by intent-to-treat analysis stratified by dose of RT at the two-sided α = 5%.
The median patient age was 70 years. Among patients, 74.8% were intermediate risk and 24.8% were high risk. In the RT arm, 407 of 409 patients received RT; in the RT plus AS arm, 403 patients received RT plus AS and three patients received RT only. At 7.2 years median follow-up, RT plus AS significantly improved biochemical DFS (HR, 0.52; 95% CI, 0.41 to 0.66; P < .001, with 319 events), as well as clinical progression-free survival (205 events, HR, 0.63; 95% CI, 0.48 to 0.84; P = .001). In exploratory analysis, no statistically significant interaction between treatment effect and dose of RT could be evidenced (heterogeneity P = .79 and P = .66, for biochemical DFS and progression-free survival, respectively). Overall survival data are not mature yet.
Six months of concomitant and adjuvant AS improves biochemical and clinical DFS of intermediate- and high-risk cT1b-c to cT2a (with no involvement of pelvic lymph nodes and no clinical evidence of metastatic spread) prostatic carcinoma, treated by radiation.
Over-irradiation Poortmans, Philip M.P; Arenas, Meritxell; Livi, Lorenzo
Breast (Edinburgh),
02/2017, Letnik:
31
Journal Article
Recenzirano
Odprti dostop
Abstract Decreasing the burden of radiation therapy (RT) for breast cancer includes, next to complete omission, several ways to tailor the extent of RT. Possible options for this include lowering of ...the total dose, such as selective omission of the boost, hypofractionated RT to shorten the duration of treatment, the selective introduction of partial breast irradiation and anatomy based target volume contouring to decrease the size of the irradiated volumes. Elective regional nodal irradiation showed in several randomised trials and meta-analyses to significantly impact on local-regional control, disease-free survival, breast cancer mortality and overall survival. The generalisability of these results remains complex in the light of the decreasing use of axillary lymph node dissection, the use of more effective adjuvant systemic therapy, the increasing use of primary systemic therapy and continuously improving RT techniques. In general, the use of RT compensates for the decreasing extent of surgery to the breast and the axillary lymph nodes, eliminating residual tumour cells while maintaining better aesthetic and functional results. In some occasions, however, the indications for the extent of RT have to be based on limited pathological staging information. Research is ongoing to individualise RT more on the basis of biological factors including gene expression profiles. When considering age, treatment decisions should rather be based on biological instead of formal age. The aim of this review article is to put current evidence into the right perspective, and to search for an appropriate appreciation of the balance between efficacy and side effects of local-regional RT.
In this study, irradiation of the internal mammary and medial supraclavicular nodes plus whole breast or thoracic-wall radiation therapy in women with localized breast cancer was linked to increased ...disease-free survival but only a marginal gain in overall survival.
The first filter stations for the lymphatic drainage of the breast are the axillary and internal mammary lymph nodes.
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Surgical studies have shown that the incidence of metastatic involvement of the internal mammary nodes varies between 4% and 9% in patients with axillary node–negative breast cancer and between 16% and 65% in patients with axillary node–positive breast cancer.
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As a consequence, surgical dissection of the internal mammary nodes was attempted but abandoned in the 1970s, since no improvement in survival was observed.
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Elective irradiation of the regional nodes remained widely used until the late 1980s, when it became . . .
Abstract Purpose To investigate the effects of using volumetric modulated arc therapy (VMAT) and/or voluntary moderate deep inspiration breath-hold (vmDIBH) in the radiation therapy (RT) of ...left-sided breast cancer including the regional lymph nodes. Materials and methods For 13 patients, four treatment combinations were compared; 3D-conformal RT (i.e., forward IMRT) in free-breathing 3D-CRT(FB), 3D-CRT(vmDIBH), 2 partial arcs VMAT(FB), and VMAT(vmDIBH). Prescribed dose was 42.56 Gy in 16 fractions. For 10 additional patients, 3D-CRT and VMAT in vmDIBH only were also compared. Results Dose conformity, PTV coverage, ipsilateral and total lung doses were significantly better for VMAT plans compared to 3D-CRT. Mean heart dose ( Dmean,heart ) reduction in 3D-CRT(vmDIBH) was between 0.9 and 8.6 Gy, depending on initial Dmean,heart (in 3D-CRT(FB) plans). VMAT(vmDIBH) reduced the Dmean,heart further when Dmean,heart was still >3.2 Gy in 3D-CRT(vmDIBH). Mean contralateral breast dose was higher for VMAT plans (2.7 Gy) compared to 3DCRT plans (0.7 Gy). Conclusions VMAT and 3D-CRT(vmDIBH) significantly reduced heart dose for patients treated with locoregional RT of left-sided breast cancer. When Dmean,heart exceeded 3.2 Gy in 3D-CRT(vmDIBH) plans, VMAT(vmDIBH) resulted in a cumulative heart dose reduction. VMAT also provided better target coverage and reduced ipsilateral lung dose, at the expense of a small increase in the dose to the contralateral breast.
Survival estimates from diagnosis are of limited importance for (ex-)breast cancer patients who survived several years, as it includes information on already deceased patients. This study analysed ...the 10-year conditional risk of recurrent breast cancer in specific prognostic subgroups. Second, we investigated 10-year conditional overall survival (OS) and relative survival (RS), adjusted for confounding.
All women diagnosed in 2005 with operated T1-2N0-1 breast cancer were selected from the Netherlands Cancer Registry. Patients were classified into T1N0, T1N1, T2N0 and T2N1 stage. Ten-year conditional recurrence rates were calculated from diagnosis, and for patients without an event (local LR, regional recurrence RR, distant metastasis DM or death) every year following diagnosis. Ten-year conditional OS was calculated using multivariable Cox regression. RS was estimated by dividing patient survival rates by those of the general Dutch population.
We included 7969 patients: 52.3% had T1N0, 15.3% T1N1, 19.9% T2N0 and 12.5% T2N1 stage. For T1N0, 10-year LR rates changed from 4.6% at diagnosis to 0.5% in year 10. RR rates changed from 2.3% to 0.2%, and DM rates changed from 7.8% to 0.6%. For T2N1 stage, the LR, RR and DM rates changed from 6.2% to 0.8%, 5.2%–0.4% and 19.6%–1.5%, respectively. For the luminal A subtype, LR, RR and DM rates changed from 3.9% to 0.4%, 1.7%–0.5% and 7.3%–1.1%, while for triple negative, these rates changed from 5.6% to 0.7%, 4.9%–0.2% and 16.7%–0%, respectively. Differences between subgroups attenuated over time, and all recurrence rates became ≤1.5% in year 10. Ten-year OS and RS, adjusted for confounding, showed declining risk differences between subgroups over time.
Differences in recurrence rates, OS and RS between prognostic subgroups declined as years passed by. These results highlight the importance of taking into account disease-free years to more accurately predict (ex-)breast cancer patients' prognosis over time.
•Survival estimates from diagnosis are less important for breast cancer survivors.•Conditional survival includes the numbers of years survived following diagnosis.•Differences in recurrence risks between prognostic subgroups declined over time.•Differences in overall and relative survival between subgroups declined as well.•Conditional survival and recurrences provide patients better insight in prognosis.
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