Letter. Intensity-modulated radiotherapy for the treatment of breast cancer

In the systematic review of intensity-modulated radiotherapy (IMRT) in the treatment of breast cancer reported in Clinical Oncology by Dayes and colleagues [1], the only prospective randomised clinical trial (n = 306) testing forward-planned IMRT to have reported a 5 year outcome for adverse effects [2] was excluded on the spurious grounds that no outcomes of interest were reported (Appendix 3). In this trial, the control arm patients were 1.7 times more likely to have a change in breast appearance than the IMRT arm patients after adjustment for the year of photographic assessment (95% confidence interval 1.2–2.5, P = 0.008)

Quantum Effects in Small-Capacitance Single Josephson Junctions

We have measured the current-voltage (I-V) characteristics of small-capacitance single Josephson junctions at low temperatures (T=0.02-0.6 K), where the strength of the coupling between the single junction and the electromagnetic environment was controlled with one-dimensional arrays of dc SQUIDs. The single-junction I-V curve is sensitive to the impedance of the environment, which can be tuned IN SITU. We have observed Coulomb blockade of Cooper-pair tunneling and even a region of negative differential resistance, when the zero-bias resistance R_0' of the SQUID arrays is much higher than the quantum resistance R_K = h/e^2 = 26 kohm. The negative differential resistance is evidence of coherent single-Cooper-pair tunneling within the theory of current-biased single Josephson junctions. Based on the theory, we have calculated the I-V curves numerically in order to compare with the experimental ones at R_0' >> R_K. The numerical calculation agrees with the experiments qualitatively. We also discuss the R_0' dependence of the single-Josephson-junction I-V curve in terms of the superconductor-insulator transition driven by changing the coupling to the environment.Comment: 11 pages with 14 embedded figures, RevTeX4, final versio

Ipsilateral breast tumour relapse: local recurrence versus new primary and the effect of whole breast radiotherapy on the rate of new primaries

PurposeThe justification for partial breast radiotherapy after breast conservation surgery assumes that ipsilateral breast tumor relapses (IBTR) outside the index quadrant are mostly new primary (NP) tumors that develop despite radiotherapy. We tested the hypothesis that whole-breast radiotherapy (WBRT) is ineffective in preventing NP by comparing development rates in irradiated and contralateral breasts after tumor excision and WBRT.Methods and MaterialsWe retrospectively reviewed 1,410 women with breast cancer who were entered into a prospective randomized trial of radiotherapy fractionation and monitored annually for ipsilateral breast tumor relapses (IBTR) and contralateral breast cancer (CLBC). Cases of IBTR were classified into local recurrence (LR) or NP tumors based on location and histology and were subdivided as definite or likely depending on clinical data. Rates of ipsilateral NP and CLBC were compared over a 15-year period of follow-up.ResultsAt a median follow-up of 10.1 years, there were 150 documented cases of IBTR: 118 (79%) cases were definite or likely LR; 27 (18%) cases were definite or likely NP; and 5 (3%) cases could not be classified. There were 71 cases of CLBC. The crude proportion of definite-plus-likely NP was 1.9% (27/1,410) patients compared with 5% (71/1,410) CLBC patients. Cumulative incidence rates at 5, 10, and 15 years were 0.8%, 2.0%, and 3.5%, respectively, for definite-plus-likely NP and 2.4%, 5.8%, and 7.9%, respectively for CLBC, suggesting a difference in the rates of NP and CLBC.ConclusionsThis analysis suggests that WBRT reduces the rate of ipsilateral NP tumors. The late presentation of NP has implications for the reporting of trials that are testing partial breast radiotherapy

The UK HeartSpare study: randomised evaluation of voluntary deep-inspiratory breath-hold in women undergoing breast radiotherapy

Purpose: to determine whether voluntary deep-inspiratory breath-hold (v_DIBH) and deep-inspiratory breath-hold with the active breathing coordinator™ (ABC_DIBH) in patients undergoing left breast radiotherapy are comparable in terms of normal-tissue sparing, positional reproducibility and feasibility of delivery.Methods: following surgery for early breast cancer, patients underwent planning-CT scans in v_DIBH and ABC_DIBH. Patients were randomised to receive one technique for fractions 1–7 and the second technique for fractions 8–15 (40?Gy/15 fractions total). Daily electronic portal imaging (EPI) was performed and matched to digitally-reconstructed radiographs. Cone-beam CT (CBCT) images were acquired for 6/15 fractions and matched to planning-CT data. Population systematic (?) and random errors (?) were estimated. Heart, left-anterior-descending coronary artery, and lung doses were calculated. Patient comfort, radiographer satisfaction and scanning/treatment times were recorded. Within-patient comparisons between the two techniques used the paired t-test or Wilcoxon signed-rank test.Results: twenty-three patients were recruited. All completed treatment with both techniques. EPI-derived ? were ?1.8?mm (v_DIBH) and ?2.0?mm (ABC_DIBH) and ? ?2.5?mm (v_DIBH) and ?2.2?mm (ABC_DIBH) (all p non-significant). CBCT-derived ? were ?3.9?mm (v_DIBH) and ?4.9?mm (ABC_DIBH) and ? ??4.1?mm (v_DIBH) and ??3.8?mm (ABC_DIBH). There was no significant difference between techniques in terms of normal-tissue doses (all p non-significant). Patients and radiographers preferred v_DIBH (p?=?0.007, p?=?0.03, respectively). Scanning/treatment setup times were shorter for v_DIBH (p?=?0.02, p?=?0.04, respectively).Conclusions: v_DIBH and ABC_DIBH are comparable in terms of positional reproducibility and normal tissue sparing. v_DIBH is preferred by patients and radiographers, takes less time to deliver, and is cheaper than ABC_DIB

Normal tissue complication probability (NTCP) parameters for breast fibrosis: pooled results from two randomised trials

Introduction: the dose–volume effect of radiation therapy on breast tissue is poorly understood. We estimate NTCP parameters for breast fibrosis after external beam radiotherapy.Materials and methods: we pooled individual patient data of 5856 patients from 2 trials including whole breast irradiation followed with or without a boost. A two-compartment dose volume histogram model was used with boost volume as the first compartment and the remaining breast volume as second compartment. Results from START-pilot trial (n?=?1410) were used to test the predicted models.Results: 26.8% patients in the Cambridge trial (5?years) and 20.7% patients in the EORTC trial (10?years) developed moderate-severe breast fibrosis. The best fit NTCP parameters were BEUD3(50)?=?136.4?Gy, ?50?=?0.9 and n?=?0.011 for the Niemierko model and BEUD3(50)?=?132?Gy, m?=?0.35 and n?=?0.012 for the Lyman Kutcher Burman model. The observed rates of fibrosis in the START-pilot trial agreed well with the predicted rates.Conclusions: this large multi-centre pooled study suggests that the effect of volume parameter is small and the maximum RT dose is the most important parameter to influence breast fibrosis. A small value of volume parameter ‘n’ does not fit with the hypothesis that breast tissue is a parallel organ. However, this may reflect limitations in our current scoring system of fibrosi

Ab initio calculation of the neutron-proton mass difference

The existence and stability of atoms rely on the fact that neutrons are more massive than protons. The measured mass difference is only 0.14\% of the average of the two masses. A slightly smaller or larger value would have led to a dramatically different universe. Here, we show that this difference results from the competition between electromagnetic and mass isospin breaking effects. We performed lattice quantum-chromodynamics and quantum-electrodynamics computations with four nondegenerate Wilson fermion flavors and computed the neutron-proton mass-splitting with an accuracy of $300$ kilo-electron volts, which is greater than $0$ by $5$ standard deviations. We also determine the splittings in the $\Sigma$, $\Xi$, $D$ and $\Xi_{cc}$ isospin multiplets, exceeding in some cases the precision of experimental measurements.Comment: 57 pages, 15 figures, 6 tables, revised versio

Superconductor-insulator quantum phase transition in a single Josephson junction

The superconductor-to-insulator quantum phase transition in resistively shunted Josephson junctions is investigated by means of path-integral Monte Carlo simulations. This numerical technique allows us to directly access the (previously unexplored) regime of the Josephson-to-charging energy ratios E_J/E_C of order one. Our results unambiguously support an earlier theoretical conjecture, based on renormalization-group calculations, that at T -> 0 the dissipative phase transition occurs at a universal value of the shunt resistance R_S = h/4e^2 for all values E_J/E_C. On the other hand, finite-temperature effects are shown to turn this phase transition into a crossover, which position depends significantly on E_J/E_C, as well as on the dissipation strength and on temperature. The latter effect needs to be taken into account in order to reconcile earlier theoretical predictions with recent experimental results.Comment: 7 pages, 6 figure