Radiation Oncology News

The standard treatment of low risk breast cancer with positive hormon receptor status is breast conserving surgery followed by endocrine therapy and adjuvant radiotherapy. Because of growing numbers of elder patients with risk of comorbidity and decreasing numbers of lokal recurrence after BCS and systemic therapy Kunkler reports about the question if RT can be omitted in defined groups of older patients.

Within the PRIME II Trial 1326 patients with unilateral breast cancer up to 3cm, N0, M0, >65 years with positive hormone receptor status, clear margins (>1mm) and without  axillary node involvement were randomized to receive (n=658) or not receive (n=668) radiotherapy after BCS with adjuvant hormone therapy. Radiation dose has been 40-50Gy in 15-25 fx.

Lokal recurrence after 5years was 4,1% vs. 1,3% in the arm without RT vs. with adjuvant RT. No diffenrence in overall survival (OS) was detected. Summing up the omission of RT is only an option in carefully selected cohorts. There is still no statement about the comorbidity  related to the use of endokrine therapy vs. the comorbidity of RT alone. Further investigation is needed.

by VHan

In this meta-analytic study (of eight randomized controlled trials including 3628 women altogether)  it was statistically test in how far  there are any benefits of EBRT after operation in regard to OS, endometrial cancer-specific survival (CSS), or distant recurrence rates in endometrial cancer at stage I. It was shown that on the one hand locoregional recurrence-rates are lower if EBRT is used but on the other hand toxicity and consequently negative effect on life quality rise in comparison with no additional treatment.

This study strictly refers to stage I endometrial cancer. A subgroup-analysis of different risk-profiles (low-, intermediate- and high-risk) within stage I could not show a significant benefit for any group. To perform this meta-analysis the investigators had to define common criteria of risk profiles because the included studies used different definitions. Limitation to the power of testing might have been caused by too small subgroup-numbers – especially in the high-risk group.The included PORTEC-2 trial analyzed the outcome of 427 women and directly compared EBRT vs. vaginal brachytherapy (VBT). In the meta-analysis VBT was grouped as “no treatment”, which should be reconsidered for clinical judgment.

By MDan

In this prospective trial it was shown that there is no evidence in favor of a Dose-Dense (DD) temozolomide therapy for Glioblastoma compared to standard dose temozolomide. The prognostic significance of the MGMT methylation status was confirmed. Toxicities ≥grade 3 were more common in the DD group.

All included patients received a radiochemotherapy with 75 mg/m² temozolomide concomitant to the irradiation. Afterwards a collective of 833 patients was randomly assigned to either a group that was treated with the standard dose of 150-200 mg/m² temozolomide on day 1-5 of a 28 days cycle or DD of 75-100 mg/m² temozolomide on day 1-21 of a 28 days cycle (arm B - 422 patients).No significant advantage in OS and in PFS was observed. Within the measured toxicity, especially leukopenia, lymphopenia and fatigue were more serious in the DD-arm. Methylated MGMT status was clearly associated with a longer OS  and a better response.The thesis that DD-schedules of temozolomide might reduce MGMT levels, exhaust activity and therefore might be of benefit for primary diagnosed GBM patients could not be confirmed by the given clinical aspects in this trial.

By Dan

The purpose of this study was to examine the association of locorgional recurrence and type of local treatment in postmenopausal patients who were treated with adequate adjuvant endocrine therapy as previously reported in the TEAM trial. Overall 9779 patients were randomized. Local treatment was breast conserving surgery plus radiotherapy (BCS + RT), mastectomy without radiotherapy (MST-only), or mastectomy plus radiotherapy (MST + RT).

As expected, more radical local therapy was associated with worse prognostic features. At a median follow-up of 5.2 years 2,9% of all patients experienced locoregional recurrences. After adjustment for prognostic factors, the risk for locoregional recurrence remained significantly higher for MST-only.

fwal

http://www.ncbi.nlm.nih.gov/pubmed/24044798

TEAM trial:

Improved target dose homogeneity and avoidance of volumes of over-dosage have been suggested to decrease toxicity of whole breast irradiation. This mono-centric trial compared acute toxicities of 100 patients with large breasts who were randomized to receive either multi beam -IMRT in supine positioning or tangential field-IMRT in prone positioning. Dose–volume parameters were assessed for the breast, heart, LAD, ipsilateral lung and contralateral breast.

Prone treatment resulted in improved dose coverage, better homogeneity, less volumes of over-dosage as well as reduced acute skin desquamation, a decrease of moist desquamation, lower incidence of dermatitis, edema, pruritus and pain. Overall a reduction of grades 2–3 toxicities was observed. Mean dose to the ipsilateral lung and the LAD were significantly lower in prone positioning.

The authors of this study see evidence to replace the supine standard treatment by prone IMRT for whole-breast irradiation in patients with large breasts.

fwal

In Summary the paper describes a multicenter trial to determine whether addition of gemcitabine to concurrent cisplatin chemoradiotherapy and as adjuvant chemotherapy with cisplatin (arm A) vs chemoradiotherapy, cisplatin 40 mg/m² on day 1 of each week for 6 weeks; and no adjuvant chemotherapy (arm B) improves PFS at 3 years in locally advanced cervical cancer. PFS at 3 years was significantly improved in arm A versus arm B (74.4% v 65.0%, respectively; P = .029), as were overall PFS (log-rank P = .0227; hazard ratio [HR], 0.68; 95% CI, 0.49 to 0.95), overall survival (log-rank P = .0224; HR, 0.68; 95% CI, 0.49 to 0.95), and time to progressive disease (log-rank P = .0012; HR, 0.54; 95% CI, 0.37 to 0.79). Grade 3 and 4 toxicities were more frequent in arm A than in arm B (86.5% v 46.3%, respectively; P < .001), including two deaths possibly related to treatment toxicity in arm A. In conclusion Gemcitabine plus cisplatin chemoradiotherapy followed by BCT and adjuvant gemcitabine/cisplatin chemotherapy improved survival outcomes with increased but clinically manageable toxicity when compared with standard treatment.

  http://www.ncbi.nlm.nih.gov/pubmed/21444871

In summary the paper describes an open-labeled randomized phase III trial which was conducted to compare paclitaxel (175 mg/m2) plus carboplatin (AUC5) followed by radiation (50.4 Gy) (experimental arm-A) versus simultaneous radiochemotherapy with cisplatin (40 mg/m2/week) (arm-B) in patients with stage IB–IIB CC after surgery. Primary objectives were PFS and OS. In conclusion sequential chemotherapy and radiation in high-risk CC could not show any significant survival benefit; however, a different toxicity profile appeared. This sequential regime may constitute an alternative option when contraindications for immediate postoperative radiation are present.

http://www.ncbi.nlm.nih.gov/pubmed/22357252

For high risk patients an adjuvant cis-platinum based radio-chemotherapy has been shown to increase OS substantially. However, the sequence and the use of different chemotherapeutic drugs have not been test in greater detail. In addition it is known that hypoxia / anemia may contribute to decrease survival rates.

Thus, Blohmer and colleagues report on the results of their randomized phase III trial including 257 patients with stage Ib to II cervical cancer after radiacal hysterectomy. In the experimental arm, four cycles of carboplatin/ ifosfamide chemotherapy and erythropoetin alfa (EPO) were followed by pelvic radiotherapy and EPO (the standard arm was using the same drugs without EPO). It could be observed that there was no statistically significant difference in recurrence-free survival (RFS) and no difference in overall survival (OS) beween both groups.  EPO can be added safely  to radiochemotherapy but is not associated with any  benefit in regard to RFS and OS.

By VHan

Archer and Pomeroy report on two of four molecularly distinct subtypes of Medulloblastoma which are associated with subtype-specific mutations. Summing up 310 primary tumors only 12 genes were recurrently mutated in these subtypes. The challange is to create targeted therapies to tend to recurring mutations across all subtypes. Novel methods and preclinical models will be needed to investigate new options thwart the hurdle of drug resistance and to develop drugs to affect the epigenetic machinery of cancer.

By VHan

Mell and colleagues report on the results of their population-based study including 58172 patients treated from 1988 to 2006 with stage I-II endometrial cancer (EC). This study was designed to estimate the cause-specific effects of adjuvant radiotherapy (RT) and lymphadenectomy (LA) on competing causes of mortality.

It could be observed that RT and LA are associated with a significant reduced noncancer mortality in stage I and II patients. Furthermore it could be assumed that improved overall survival reported from SEER studies may be attributed to a more selective application of lymph-node dissection in healthier patients.

 By VHan

Although the effectiveness of RT on LC and OS in node positive patients has been confirmed, the role of internal mammary nodes (INM) irradiation has been controversial. This prospective trial included 1334 patients from 01/1991-12/1997 with newly diagnosed stage I/II adenocarcinoma of the breast who underwent mastectomy and who also had positive axillary nodes or a medial/central tumor with/without axillary LN involvement. No significant benefit of IMN irradiation could be demonstrated: the 10-year OS was 59.3% in the IMN-RT-  group and 62.6% in the IMN-RT+ group. There was no significant increase in late cardiac toxicity in the IMN-RT+ group (15% vs. 11%).

Since this study was designed to show a 10% OS benefit, a lower advantage in OS cannot be excluded and certain subgroups (medial/central tumor, positive axillary LN) may benefit from IMN-RT. Larger studies are needed to demonstrate the forementioned benefit.

By CAnd

Prostate cancer is well known for it’s low growth fraction, slow proliferation, and a long potential doubling time. Furthermore the adjacent normal tissues have been characterized to have a low α/β ratio (α= the linear component of cell survival curve, low dose area; β = the quadratic component of the cell survival curve, high dose area). The α/β ratio of prostate cancer is estimated at 1,5Gy (compared to >3Gy for the normal tissues, >5Gy for rectum). This low a low α/β ratio indicates a greater sensitivity to higher radiation doses per fraction (hypofractionation).

The purpose of this trial was to determine whether a hypofractionated escalated radiation dose significantly reduced biochemical and/or clinical disease failure (BCDF) in men treated primarily for prostate cancer. Between June 2002 and May 2006, 307 men with intermediate and high-risk prostate cancer were randomly assigned to conventional fractionation intensity-modulated radiation therapy (CIMRT; 153 patients) versus hypofractionated IMRT (HIMRT; 154 patients). The CIMRT group received 76Gy in 38 fractions á 2 Gy, on the other side the HIMRT group received 70,2Gy in 26 fractions á 2,7Gy, which is equivalent to 84,4Gy á 2Gy. In addition, patients with high-risk prostate cancer were also treated with long-term androgen deprivation therapy (ADT), meanwhile the intermediate risk prostate patients received short term ADT. The primary end point was the cumulative incidence of BCDF. The toxicity was also assessed.

There was no statistically significant difference in 5-year rates of BCDF between both arms (21,4% for CIMRT and 23,3% for HIMRT). The distant and local failure, and prostate cancer specific mortality were also found to be similar for CIMRT and HIMRT. The toxicity, in term of late toxicity of gastrointestinal and genitourinary, was not statistically different between the arms. Nevertheless patients with compromised urinary function before the therapy began, had significantly worse function after HIMRT.

Hence, HIMRT did not significantly reduced BCDF. Some factors might contribute to this result, such as heterogeneity of prostate cancer, hypoxia, or the use of ADT as an adjunct to radiation. Furthermore, there is a probability that the α/β ratio of prostate cancer is >1,5.  However there is one benefit of HIMRT, which is the therapy can be performed in fewer weeks (5 weeks versus 7,5 weeks in CIMRT).

http://www.ncbi.nlm.nih.gov/pubmed/24101042

Radical transurethral resection of bladder tumor (TURBT) followed by radiochemotherapy (trimodality treatment) has demonstrated to have similar outcomes in comparison with radical cystectomy by patients with muscle invasive bladder cancer.

The initial radiation treatment volume included the pelvic lymph node (LN) in radiation portals. It was based on the knowledge from cystectomies series, that micrometastasis was found in 25-44% of the cases in the pelvic LN. However, since the newer chemotherapy agents (gemcitabine and paclitaxel) have been used as concurrent or neoadjuvant to the radiation, there is an ongoing debate by patients with negative LN, whether to irradiate the pelvic LN or not. Excluding the pelvic LN in those patients would minimize the bowel toxicity.

230 patients with histologically confirmed muscle invasive bladder cancer and negative LN (T2-T4N0M0) were recruited. All had maximal TURBT and were were randomly treated with whole pelvic concurrent chemoradiation (WP-CCRT: 120 patients) and bladder only concurrent chemo radiation (BO-CCRT: 110 patients).

The median follow-up was 5 years. WP-CCRT had a 5-year disease-free survival of 47,1% compared with 46,9% in BO-CCRT. The bladder preservations rates were 58,9% in WP-CCRT and 57,1% in BO-CCRT. The 5-years OS were 52,9% in WP-CCRT patients and 51% in BO-CCRT.

With these similar results, BO-CCRT may be used for patients with muscle invasive, LN negative bladder cancer, in order to reduce the side effects of CCRT. However this study didn’t consider important prognostic factors locoregional and systemic recurrence, such lmyphovascular involvement, her-2 neu overexpression, or tumor grade.

http://www.ncbi.nlm.nih.gov/pubmed/21945107

The role of axillary surgical and non-surgical interventions in breast cancer treatment has changed drastically over the last decades. This study summarizes evidence and shows mortality and morbidity outcomes in patients with breast cancer in regard to different strategies of axillary clearance.

Several databases were searched. There were randomized and non-randomized trials included, non-randomized trials were only included if the patients had breast cancer, underwent surgery and had a follow-up in at least 50% of the patients undergoing treatment including surgery or radiation of the axillary nodes. Follow-up time of the studies had to be at least 2 years. In the end 17 of 1070 studies were included in this review.

End points of the study were isolated recurrence of axillary lymph node metastases, complication rates and survival with the different surgical techniques and interventions.

In patients with no palpable lymph nodes, complete axillary node dissection shows no survival benefit but reduces the risk of recurrence of axillary node metastases compared to SLN biopsy.

 All in all the available data lead to the assumption that axillary node dissection may create more negative effects in terms of morbidity than is is associated with benefit in terms of cancer control patients with breast cancer having breast-conserving therapy without having suspicious lymph nodes.

http://www.ncbi.nlm.nih.gov/pubmed/24084924