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Primary testicular lymphoma (PTL) is a rare, clinically aggressive form of extranodal lymphoma. The vast majority of cases are histologically diffuse large B-cell lymphoma, but rarer subtypes are clinically important and must be recognized. In this review, we discuss the incidence, clinical presentation, and prognostic factors of PTL and present a summary of the recent advances in our understanding of its pathophysiology, which may account for the characteristic clinical features. Although outcomes for patients with PTL have historically been poor, significant gains have been made with the successive addition of radiotherapy (RT), full-course anthracycline-based chemotherapy, rituximab and central nervous system–directed prophylaxis. We describe the larger retrospective series and prospective clinical trials and critically examine the role of RT. Although rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone given every 21 days with intrathecal methotrexate and locoregional RT is the current international standard of care, a substantial minority of patients progress, representing an unmet medical need. Finally, we discuss new treatment approaches and recent discoveries that may translate into improved outcomes for patients with PTL.

Distributed energy technologies, such as residential energy storage, embedded generation, and microgrids, are likely to play an increasing role in future energy systems. Getting the most value from these distributed assets is often dependent on the ability to optimize their operation in a distributed manner. This distributed optimization, in turn, calls for effective short-term forecasts of the output of small-scale generating assets, and the demand of small-scale aggregations of users. This paper introduces the integration of data-driven forecasting and operational optimization methods into a single model, avoiding the need to explicitly produce forecasts. The method is tested against two empirical energy storage operational optimization problems, the minimization of peak energy drawn by a small aggregation of customers, and the minimization of the energy costs of a collection of households which have rooftop PV systems. The integrated forecasting and operational optimization approach performs well at the peak demand minimization problem for intermediate-sized aggregations (50 residential customers or more), while an approach with separate forecasting and optimization performed better on the energy cost minimization problem. These results suggest that the integrated approach can be effective in applications where (i) forecasting difficulty is intermediate, and (ii) the exact operational optimization formulation can be well approximated by a data-driven model trained on a small fraction of the available forecast training data.

Background Approximately half of patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL) will relapse despite curative intent therapy with salvage chemotherapy (SC) and autologous stem cell transplantation (ASCT). Consolidative radiotherapy (cRT) is used to reduce the risk of local relapse in high risk patients. We aimed to examine the (i) impact of cRT on outcomes, (ii) role of positron-emission tomography computerised tomography (PET-CT) imaging in predicting outcomes, (iii) identify a subgroup most likely to benefit from cRT, (iv) assess patterns of relapse to understand the mechanisms of treatment failure and (v) propose a PET-CT based risk stratification model for relapse. Patients and Methods 104 patients with R/R cHL treated with curative intent SC and ASCT between January 2000 and May 2019 were retrospectively identified from two sites in Melbourne, Australia. Fifty-six patients (54%) received peri-transplant cRT. SC consisted of chemotherapy and/or immunotherapy of the clinician's choice followed by interim assessment by PET-CT imaging. Patients with a complete or partial metabolic response proceeded to ASCT. Disease status was routinely evaluated by physical examination and PET-CT imaging at time of disease relapse, at completion of salvage chemotherapy, and at three months following ASCT. A complete metabolic response on fluorodeoxyglucose (FDG) PET/CT was defined by Deauville Score ≤3 (uptake ≤ liver, PET negative) and compared to Deauville Score ≥4 (PET positive). Results With a median follow-up of 2.5 (range 0.2-15.2) years, the 2-year progression free survival (PFS) and overall survival (OS) rates were 68.3% and 83.6%, respectively. Inferior PFS was associated with advanced stage (III or IV) disease at relapse (AS-R) (53% vs 78%; P=0.004) and PET positivity after SC (51% vs 79%; P=0.005). Compared to PET negative patients after SC, 2-year PFS was significantly inferior in patients who were PET positive and did not receive cRT (38% vs 79%; P Conclusion One third of patients with relapsed/refractory cHL who received SC and ASCT subsequently relapsed within two years. cRT may abrogate the negative predictive value of a positive PET scan after SC, of which patients with LS-R are most likely to benefit. PET positive disease and residual mass ≥2cm after SC are associated with inferior PFS despite the use of cRT. Conversely, patients who are PET negative without residual tumor mass after SC have superior outcomes. cRT is associated with improved local disease control, yet approximately half of patients who relapse after cRT will still have in-field relapse, possibly warranting the evaluation of higher cRT doses. Therefore, we propose a PET-based model which may identify the patients at "high" risk of progressing after ASCT who are most likely to benefit from clinical trials examining different modalities of consolidative therapy (Figure 1D). Validation of this model is required in a larger independent population. Disclosures Ritchie: Amgen: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy; BMS: Research Funding; Takeda: Research Funding; Beigene: Research Funding; Imago: Research Funding; Novartis: Honoraria; Sanofi: Honoraria. MacManus:National Health and Medical Research Council Australia: Research Funding. Seymour:Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Honoraria; Acerta: Consultancy, Honoraria. Dickinson:GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding, Speakers Bureau; Merck Sharpe and Dohme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

In various manufacturing and computing environments there may be certain time intervals, during which processing may continue but may not be initiated. We examine the problem of off-line scheduling in the presence of such forbidden zones. The problem is closely related to a one-dimensional open-end bin packing problem. We prove that the decision version of the problem is strongly NP-complete and then establish bounds on the asymptotic performance ratio of an O(nlogn) approximation algorithm for a special case, and test it numerically. We present a further heuristic for a non-regular case and test it empirically.

This paper presents and empirically evaluates two approaches to accounting for forecast uncertainty when attempting to optimize the operation of a residential battery energy storage system. Data-driven methods are used for forecasting, and dynamic programming, within a receding horizon controller, is used for operational optimization. The first method applies a discount factor to costs incurred at later intervals in a deterministic dynamic programming control horizon, provided with point forecasts. In the second approach probabilistic (scenario) forecasts are generated using Lloyd-Max quantization of the distribution of forecast errors, to allow the use of a stochastic dynamic programming formulation. These methods are applied to maximizing the cost-savings delivered from a residentially owned and operated battery, using a case-study of residential consumers with roof-top PV systems in New South Wales, Australia. It is found that scenario forecasts can offer an 8% increase in annual cost-savings, on average, when using a univariate multiple linear regression forecast.

Extranodal NK/T-cell lymphoma, nasal type (EN-NK/TCL-NT) is rare in the Western world. We launched the current single-institutional retrospective study with Institutional Review Board approval to better understand the disease. 43 EN-NK/TCL-NT patients treated from 1996 to 2014 were analyzed, including 10 (23%) Asians and 33 (76%) non-Asians. 19/26 (73%) early-stage patients received short-course chemotherapy followed by radiotherapy. 14/17 (82%) advanced-stage patients received primary chemotherapy. Complete response rate was significantly higher in the modified-SMILE group than the accelerated-CHOP group (80% vs. 30%, p= 0.015). The 2-year overall survival (OS) and progression-free survival (PFS) were 60% and 40% respectively. Early-stage disease had significantly higher 2-year OS (87% vs. 21%) and PFS (56% vs.18%) than advanced-stage (p

Marginal zone lymphoma (MZL) is a radiosensitive tumor, with high local control (LC) rates with moderate dose radiotherapy (RT). This retrospective study, performed at the Peter MacCallum Cancer Centre, evaluated the efficacy and toxicity of patients with orbital MZL treated to 24-25 Gy. Twenty-four patients (27 orbits) were identified, with median follow-up of 41 months. Disease was conjunctival in 16 orbits (59%), lacrimal in seven (26%), in the eyelid in one (4%) and elsewhere in three (11%). All patients attained a complete response. Three patients had treatment failures: one local relapse, one contralateral and one distant relapse. Freedom from local failure, freedom from progression, progression-free survival and overall survival were 100%, 90%, 90% and 100% at 2 years and 92%, 81%, 81% and 100% at 5 years, respectively. Aside from cataractogenesis, there was no significant late toxicity. Our study shows that RT doses of 24-25 Gy provide high rates of LC for orbital MZL with acceptable morbidity.

Purpose To systematically review the evidence for the radiotherapeutic and surgical management of patients newly diagnosed with intraparenchymal brain metastases. Methods and Materials Key clinical questions to be addressed in this evidence-based Guideline were identified. Fully published randomized controlled trials dealing with the management of newly diagnosed intraparenchymal brain metastases were searched systematically and reviewed. The U.S. Preventative Services Task Force levels of evidence were used to classify various options of management. Results The choice of management in patients with newly diagnosed single or multiple brain metastases depends on estimated prognosis and the aims of treatment (survival, local treated lesion control, distant brain control, neurocognitive preservation). Single brain metastasis and good prognosis (expected survival 3 months or more): For a single brain metastasis larger than 3 to 4 cm and amenable to safe complete resection, whole brain radiotherapy (WBRT) and surgery (level 1) should be considered. Another alternative is surgery and radiosurgery/radiation boost to the resection cavity (level 3). For single metastasis less than 3 to 4 cm, radiosurgery alone or WBRT and radiosurgery or WBRT and surgery (all based on level 1 evidence) should be considered. Another alternative is surgery and radiosurgery or radiation boost to the resection cavity (level 3). For single brain metastasis (less than 3 to 4 cm) that is not resectable or incompletely resected, WBRT and radiosurgery, or radiosurgery alone should be considered (level 1). For nonresectable single brain metastasis (larger than 3 to 4 cm), WBRT should be considered (level 3). Multiple brain metastases and good prognosis (expected survival 3 months or more): For selected patients with multiple brain metastases (all less than 3 to 4 cm), radiosurgery alone, WBRT and radiosurgery, or WBRT alone should be considered, based on level 1 evidence. Safe resection of a brain metastasis or metastases causing significant mass effect and postoperative WBRT may also be considered (level 3). Patients with poor prognosis (expected survival less than 3 months): Patients with either single or multiple brain metastases with poor prognosis should be considered for palliative care with or without WBRT (level 3). It should be recognized, however, that there are limitations in the ability of physicians to accurately predict patient survival. Prognostic systems such as recursive partitioning analysis, and diagnosis-specific graded prognostic assessment may be helpful. Conclusions Radiotherapeutic intervention (WBRT or radiosurgery) is associated with improved brain control. In selected patients with single brain metastasis, radiosurgery or surgery has been found to improve survival and locally treated metastasis control (compared with WBRT alone).

Smart grids utilise omnidirectional data transfer to operate a network of energy resources. Associated technologies present operators with greater control over system elements and more detailed information on the system state. While these features may improve the theoretical optimal operating performance, determining the optimal operating strategy becomes more difficult. In this paper, we show how a decision tree ensemble or ‘forest’ can produce a near-optimal control strategy in real time. The approach substitutes the decision forest for the simulation–optimisation sub-routine commonly employed in receding horizon controllers. The method is demonstrated on a small and a large network, and compared to controllers employing particle swarm optimisation and evolutionary strategies. For the smaller network the proposed method performs comparably in terms of total energy usage, but delivers a greater demand deficit. On the larger network the proposed method is superior with respect to all measures. We conclude that the method is useful when the time required to evaluate possible strategies via simulation is high.

Chemotherapy plus radiotherapy is the standard of care for patients with limited stage Hodgkin lymphoma (HL). Radiotherapy is evolving from involved field radiotherapy (IFRT) to involved node radiotherapy (INRT) to decrease radiotherapy-related morbidity. In the absence of long-term toxicity data, dose-volume metrics of organs at risk (OAR) provide a surrogate measure of toxicity risk.Ten female patients with stage I-IIA supradiaphragmatic HL were randomly selected. All patients had pre-chemotherapy computerised tomography (CT) and CT-positron emission tomography staging. Using CT planning, three radiotherapy plans were produced per patient: (i) IFRT, (ii) INRT using parallel-opposed beams and (iii) INRT using volumetric modulated arc therapy (VMAT). Radiotherapy dose was 30.6 Gy in 1.8 Gy fractions. OAR evaluated were lungs, breasts, thyroid, heart and coronary arteries.Compared with IFRT, INRT significantly reduced mean doses to lungs (P0.01), breasts (P0.01), thyroid (P0.01) and heart (P0.01), on Wilcoxon testing. Compared with conventional INRT, VMAT improved dose conformality but increased low-dose radiation exposure to lungs and breasts. VMAT reduced the heart volume receiving 30 Gy (V30) by 85%.Reduction from IFRT to INRT decreased the volumes of lungs, breasts and thyroid receiving high-dose radiation, suggesting the potential to reduce long-term second malignancy risks. VMAT may be useful for patients with pre-existing heart disease by minimising further cardiac toxicity risks.

Background Few studies have examined the factors that predict information seeking by cancer patients. This study investigated the influence of different styles of adjustment to cancer, information goals and information needs on the information seeking by lung cancer patients. Method Lung cancer patients were recruited at their first appointment with their radiation oncologist and completed two questionnaires, one month apart, containing the Patient Information Needs Questionnaire, Mini-Mental Adjustment to Cancer Scale, the number of information sources accessed and a purpose-built measure of cancer-related personal goals. Results Fifty-nine participants completed two questionnaires. The average number of information sources accessed by participants increased over the 1-month period, from 7.2 to 9.1 sources (p = 0.026). Information goals at time 1 predicted information seeking at time 2 (p = 0.014). Information needs at time 1 did not predict information seeking at time 2 (Disease Orientated information need p = 0.084, Action Orientated information need p = 0.229). Cognitive Avoidance at time 1 was negatively associated with the number of information sources accessed at time 2 (p = 0.046). This relationship became a non-significant trend (p = 0.066) when baseline information seeking was controlled for. No other adjustment style (at time 1) exhibited a significant relationship with information seeking at time 2. Conclusions These findings suggest that information seeking may vary as a function of adjustment to cancer. Consequently, information provision to patients could be more appropriately tailored by attending to how a patient is adjusting to their diagnosis of cancer. Copyright © 2012 John Wiley & Sons, Ltd.

The query complexity of estimating the mean of some [0, 1] variables is understood. Inspired by some work by Carterette et al. on evaluating retrieval systems, and by Moffat and Zobel’s new proposal for such evaluation, we examine the query complexity of weighted average calculation. In general, determining an answer within accuracy $${\varepsilon}$$, with high probability, requires $${\Omega(\varepsilon^{-2})}$$ queries, as the mean is a special case. There is a matching upper bound for the weighted mean. If the weights are a normalized prefix of a divergent series, the same result holds. However, if the weights follow a geometric sequence, a sample of size $${\Omega(\log (1/\varepsilon))}$$ suffices. Our principal contribution is the investigation of power-law sequences of weights. We show that if the ith largest weight is proportional to i −p , for p > 1, then the query complexity is in $${\Omega(\varepsilon^{2/(1-2p)})}$$.

Objective: Although typically high, the need for information varies between cancer patients. Few studies, however, have examined the factors that predict patient information needs. This study investigated the influence of different styles of adjustment to cancer on information needs. It was proposed that adjustment styles can be defined in terms of goal pursuit and that adjustment influences information needs as these also arise from goal pursuit. Method: Seventy-three lung cancer patients were recruited at their first appointment with their radiation oncologist. Participants completed the Patient Information Needs Questionnaire measuring Disease Orientated (DO) information and Action Orientated (AO) information, the Mini-Mental Adjustment to Cancer Scale, and a purpose-built measure of cancer-related personal goals. Results: High levels of the adjustment styles, Fighting Spirit and Anxious Preoccupation, were related to a high need for DO information (p=0.042 and 0.023, respectively). Conversely, high levels of the adjustment style Cognitive Avoidance was related to a low need for DO information (p=0.041). High levels of Anxious Preoccupation were also positively related to a high need for AO information (p=0.018). Support for the proposed theoretical model was also found: information goals predicted information needs and mediated the relationship between Fighting Spirit and DO information need. Conclusions: These findings suggest that information needs vary as a function of adjustment to cancer. Consequently information provision to cancer patients could be more appropriately tailored by attending to how a patient is adjusting to their diagnosis of cancer. Copyright © 2010 John Wiley & Sons, Ltd.

The frequency of adjustments to the supply temperature set-point in district heating networks influences the overall operating cost in two ways: adaptability to changes in network conditions; and availability of time for determining an appropriate response. In this paper we investigate this trade-off and show that operating costs can be reduced through appropriate control period selection. Eleven hypothetical scenarios spanning five different networks have been simulated under a variety of control policies. When compared to a constant supply temperature strategy, the best policy in each case achieved a loss reduction of 5–24%.

This article considers short-term energy management of a wind power plant with battery storage, in order to smooth the variations of power output to the external grid. An optimal online heuristic is developed for a control environment, in which decision making is independent of wind historical data and forecasts.

In this paper, we consider the on-line scheduling of two parallel identical machines sharing a single server with the objective of minimizing the latest completion time of all jobs. Each job has to be setup by the server before being processed on one of the machines. Three special cases: equal length jobs, equal processing times and regular equal setup times are considered and the asymptotic competitive ratios of list scheduling are determined. Also, a lower bound for the equal length job case is given, and two heuristics with tight asymptotic competitive ratios for the other two cases are proposed.

We study a class of scheduling problems with batch setups for the online-list and online-time paradigms. Jobs are to be scheduled in batches for processing. All jobs in a batch start and complete together, and a constant setup is prior to each batch. The objective is to minimize the total completion time of all jobs. We primarily consider the special cases of these problems with identical processing times, for which efficient on-line heuristics are proposed and their competitive performance is evaluated.

We consider the problem of on-line scheduling with non-crossing constraints. The objective is to minimize the latest completion time. We provide optimal competitive ratio heuristics for the on-line list and on-line time problems with unit processing times, and a 3-competitive heuristic for the general on-line time problem.

Summary The risk of breast cancer following radiotherapy for Hodgkin’s lymphoma appears to be dose related. In this study we compared breast dose in an anthropomorphic phantom for conventional ‘mantle’; upper mediastinal/bilateral neck (minimantle) and unilateral neck fields, and evaluated the accuracy of computer planned dose estimates for out-of-field doses. For each field, computer-planned breast dose (CPD) estimates were compared with thermoluminescence dosimetry measurements in five locations within ‘breast tissue’. CPD were also compared with ion chamber measurements in a slab phantom. Measured dose and CPD were within 20% of each other up to approximately 10 cm from the field edge. Beyond 10 cm, the CPD underestimated dose by a factor of 2 or more. The mini-mantle reduced the breast dose by a factor of approximately 10 compared with the mantle treatment. Treating the neck field lowered the breast dose by a further 50% or more. Modern involved-field radiotherapy for lymphoma substantially reduces breast dose compared with mantle fields. Computer dosimetery underestimated dose at larger distances from the field. This needs to be considered if computer dosimetery is used to estimate breast dose and, by extrapolation, breast cancer risk.

Purpose Accurate staging is critical to select patients with early-stage (I–II) follicular lymphoma (ESFL) suitable for involved-field radiotherapy (IFRT) and to define the radiotherapy portal. We evaluated the impact of fluorodeoxyglucose (FDG) PET on staging, treatment, and outcome for patients with ESFL on conventional staging. Methods and Materials Forty-two patients with untreated ESFL (World Health Organization Grade I–IIIa, or “low grade”) following a minimum of physical examination, computerized tomography, and bone marrow examination (conventional assessment) and who had staging PET from June 1997 to June 2006 were studied retrospectively. Stage allocation was based on routine imaging reports. Disease sites, stage, and management plan were recorded based on conventional assessment or conventional assessment plus PET. Results FDG avidity was demonstrated in 97% of patients in whom disease was evident on conventional assessment after biopsy. PET findings suggested a change of stage or management in 19 patients: 13 (31%) who were upstaged to Stage III–IV, altering ideal management from IFRT to systemic therapy, and 6 (14%) who had the involved field enlarged, including 4 upstaged from Stage I to II. Of these 19 cases, PET findings were considered true positive in 8 patients, indeterminate in 10, and false positive in only 1 patient. Conclusions Our data confirm that ESFL is usually FDG-avid. In routine practice, PET has the potential to upstage and thereby alter management in a high proportion of patients with apparent ESFL.

Heuristic performance has been mainly measured by effectiveness (near optimality) and efficiency (computational complexity). More recently researchers have begun the difficult task of evaluating heuristic stability, or sensitivity, to perturbations in the problem specifications. Various stability measures have been proposed. Here we consider how Spearman's footrule, a measure of permutation disarray, may shed some further light on this, not as yet well understood, problem.

Introduction Evidence that has been published in the last decade indicates that in patients with limited-stage small-cell lung cancer (SCLC), hyperfractionated accelerated thoracic radiotherapy (RT) given twice daily and prophylactic cranial irradiation (PCI) have each separately improved survival. Concerns about the toxicities associated with these treatments and uncertainty about their impact on survival outside the trial setting may have restricted the extent to which they have been incorporated into standard treatment protocols. We have reviewed the experience at Peter MacCallum Cancer Centre to determine the tolerability of these treatments in routine practice and to determine their effects on survival. Methods A retrospective review of patients with limited-stage SCLC receiving a radical course of thoracic RT between June 1998 and May 2002, including either conventional fractionation at 50 Gy for 5 weeks, or hyperfractionated accelerated RT at 45 Gy for 3 weeks. Patients achieving a complete response were offered PCI at 36 Gy in 18 fractions. The main outcomes recorded were RT toxicity (graded using CTCAE v. 3.0 and RTOG/EORTC late scoring criteria), response, relapse-free survival, and overall survival. Results Ninety patients were identified as having undergone radical-intent thoracic RT, with a median potential follow-up of 4.2 years. Fifty-seven patients (63%) were treated with hyperfractionated accelerated RT, and 33 (37%) were treated with conventional fractionation. Forty-six patients (51%) received PCI. Patients receiving hyperfractionated accelerated RT compared with conventional fractionation had higher rates of grade 3 and 4 esophagitis (14% versus 6%; p = 0.312), a higher rate of treatment interruptions (12% versus 3%; p = 0.250), and a higher hospital admission rate (39% versus 15%; p = 0.031). The majority of patients were able to complete the planned treatment, and there were no treatment-related deaths. Median survival for all patients from commencement of RT was 14.2 months (95% confidence interval [CI]: 11.9–18.1 months), and survival at 2 years was 24.8% (95% CI: 16.9–35.0%). On multifactor analysis, the only factor associated with longer survival was PCI (hazard ratio=0.40; p Conclusions Hyperfractionated accelerated RT was more toxic than conventional fractionation, but it was possible to deliver treatment as planned in the majority of patients. PCI was associated with improved survival. Both treatments can be incorporated into routine practice.

Background: We evaluated the efficacy and toxicity of radiotherapy (RT) in patients with low-grade gastric marginal zone lymphoma. Methods: A retrospective review of consecutive cases of gastric marginal zone lymphoma treated by radical RT at the Peter MacCallum Cancer Centre and Radiation Oncology Victoria between January 1980 and September 2003 was carried out. Results: Eighteen patients (11 men and 7 women) were identified. The median age at commencement of RT was 65 years (range 42–84 years). Prior treatment included Helicobacter pylori eradication in 12 patients, chemotherapy in 7 and surgery in 2, whereas 2 patients had no prior therapy. The median time to progression after commencement of last treatment before RT was 4.8 months (range 0–129.4 months). The radiation fields included the stomach plus perigastric and coeliac nodes in 15 patients (83%), stomach plus spleen in 2 patients (11%) and stomach plus para-aortic nodes in 1 patient (6%). The median RT dose was 30 Gy (range 30–36 Gy) in a median 20 fractions (range 17–24 fractions). One patient required treatment interruption for acute toxicity. A complete response on post-RT biopsies was achieved in 17 of 18 patients (94%). With a median follow up of 4.5 years after RT, 3 of these 17 patients (18%) have had a recurrence. At the last follow up, 11 patients were alive in continuous complete histological remission. No late renal toxicity was identified. Conclusion: Radiotherapy is an effective, well-tolerated treatment for patients with low-grade gastric marginal zone lymphoma, including those who have had prior therapy.

Residual 2-fluoro-2-deoxyglucose (FDG) - positron emission tomography (PET) positivity during treatment of patients with diffuse large B-cell lymphoma (DLBLC) prospectively identifies a subgroup at high likelihood of subsequent treatment failure. A single institution clinical audit of FDG-PET performance for this indication was undertaken for patients with DLBCL treated with anthracycline-based chemotherapy +/- radiotherapy. Of 45 eligible patients, 14 (31%) were PET-positive after a median of three chemotherapy cycles (range 1 - 5), of which 10 (71%) progressed at a median of 6.5 months. An interim positive PET was a statistically significant adverse prognostic factor for treatment failure (P0.0001, log-rank analysis) with a hazard ratio for a positive interim-treatment PET of 9 (95% confidence interval = 4 - 55) and positive predictive value of 71% and negative predictive value of 90%. Notably, four patients with low-grade FDG-avidity limited to sites previously involved by biopsy-proven osseous lymphoma, remain progression-free (median follow-up 62 months). Low-grade FDG-avidity on interim restaging at sites of bone involvement by DLBCL at diagnosis, appears to be less predictive of disease progression than residual nodal or extra-nodal soft tissue abnormality by PET.

We evaluated the effect of adjuvant whole brain irradiation (WBI) after surgery or radiosurgery for solitary brain metastases in a Phase III multicentre trial with randomization to 30-36 Gy WBI or observation. The study was closed early due to slow accrual after 19 patients (WBI 10, observation 9). There was no difference in CNS failure-free survival or overall survival between the arms. There was a trend to reduced CNS relapse with WBI (30% versus 78%, P=0.12). Limited analysis of quality of life and neurocognitive function data revealed no evidence of difference between the arms. Our results are not inconsistent with two larger randomized trials and support the use of upfront WBI to decrease brain recurrence in this setting.

In order to illustrate how various areas of operations research interact in an actual manufacturing scenario, we propose the use of a strawberry jam-making supply chain model consisting of an inventory partner, a production scheduling partner and a delivery partner. The problem is to minimise the overall supply chain cost consisting of inventory order cost, inventory unit purchasing cost, inventory storage cost, transport booking cost, jam storage cost, delivery travel distance cost and jam arrival earliness and tardiness costs. We report on how we devised and taught this case to First Year Mechanical and Manufacturing Engineering students at the University of Melbourne.

This paper considers the problem of scheduling two-operation non-preemptable jobs on two identical semi-automatic machines. A single server is available to carry out the first (or setup) operation. The second operation is executed automatically, without the server. The general problem of makespan minimization is NP-hard in the strong sense. In earlier work, we showed that the equal total length problem is polynomial time and we also provided efficient and effective solutions for the special cases of equal setup and equal processing times. Most of the cases analyzed thus far have fallen into the category of regular problems. In this paper we build on this earlier work to deal with the general case. Various approaches will be considered. One may reduce the problem to a regular one by amalgamating jobs, or we may apply the earlier heuristics to (possibly regular) job clusters. Alternately we may apply a greedy heuristic, a metaheuristic such as a genetic algorithm or the well known Gilmore-Gomory algorithm to solve the general problem. We report on the performance of these various methods.

The majority of renewable energy sources are non-dispatchable, meaning that it is not possible to control when and how much power they produce. For non-dispatchable renewable energy sources to meet a greater proportion of global electricity demand, the industry must develop and implement strategies that directly address the intermittency challenge. This paper considers electrical storage and transmission assets as alternative means of matching non-dispatchable generation with non-deferrable demand. It seeks an optimal combination of storage and transmission assets for a simplified representation of Australian population centres, assuming that demand is met entirely with solar PV generation. This problem is solved using a Mixed Integer Linear Program. Under the baseline assumptions it is found that the optimal (lowest cost) solution has significant quantities of storage in all load centres, as well as transmission assets installed over large distances. The storage selected was 10–15% Li-ion batteries by energy; with the remainder being pumped hydro storage.

BACKGROUMD. The curative potential of radiotherapy CRT) alone as initial treatment for patients with Stage I-II lymphocyte-predominant Hodgkin lymphoma (LPHL) has not been defined well. METHODS. Two hundred two patients who were treated between 1969 and 1995 were evaluated in a retrospective, multicenter study. RESULTS. Patient characteristics were as follows: The median age was 31 years, 75% of patients were male, 80% of patients had Ann Arbor Stage I disease, 1% of patients had bulky disease, 3% of patients had B symptoms, 1% of patients had extranodal involvement, and 80% of patients had supradiaphragmatic disease. The RT fields were a full mantle field in 52% of patients, less than a full mantle field in 24% of patients, an inverted-Y field in 17% of patients, less than an inverted-Y field in 3% of patients, and total lymph node irradiation in 3% of patients. The median dose was 36 Gray. The median follow-up was 15 years. The overall survival (OS) rate at 15 years was 83%, and freedom from progression (FFP) was observed in 82% of patients, including 84% of patients with Stage I disease and 73% of patients with Stage II disease. No recurrent LPHL and only 1 patient with non-Hodgkin lymphoma (NHL) were reported after 15 years. Adverse prognostic factors that were identified on multifactor analysis were as follows: for OS, age 45 years or older (P < 0.0005), the presence of B symptoms (P = 0.002), increasing number of sites (P = 0.015); for FFP, increasing number of sites (P= 0.002). No significant difference was found in FFP in a comparison of patients who received elective mediastinal RT with patients who did not receive mediastinal RT (P = 0.11). Causes of death at 15 years were LPHL in 3% of patients, NHL in 2% of patients, in-field malignancy in 2% of patients, in-field cardiac/respiratory in 4% of patients, and other in 6% of patients. CONCLUSIONS. The current data suggested that RT potentially may be curative for patients with Stage I-II LPHL and raise the possibility that limited-field RT may be used without loss of treatment efficacy. Involved-field RT warrants further inves-tigation for patients with early-stage LPHL.

We consider the scheduling of N jobs divided into G families for processing on M identical parallel machines. No set-up is necessary between jobs belonging to the same family. A set-up must be scheduled when switching from the processing of family i jobs to those of another family j, i ≠ j, the duration of this set-up being the sequence-independent set-up time sj for family j. We propose heuristics for this problem and computationally evaluate the performance of the heuristics relative to lower bounds and solutions obtained using an exact algorithm.

Summary Background: We previously reported that F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) response correlated strongly with survival after radical radiotherapy (RT)/chemoradiotherapy for non-small cell lung cancer (NSCLC). PET-response, survival and patterns of failure data are presented with long-term follow-up. Methods: Pre- and post-treatment FDG–PET scans were performed for 88 patients after concurrent platinum-based radical chemo/RT ( n = 73) or radical RT alone ( n = 15). PET responses were prospectively assessed as either complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), or progressive metabolic disease (PMD). Results: RT was 60Gy in 30 fractions in 6 weeks. Follow-up PET was performed at a median of 70 days after treatment. PET responses were: CMR, n = 40 (45%); PMR, n = 32 (36%); SMD, n = 5 (6%) and PMD 11 (13%). Estimated median survival after follow-up PET was 23 months; median follow-up duration 35 months. One and 2 year survival after follow-up PET was 68% and 45%, respectively. Median survival for CMR and non-CMR patients was 31 and 11 months, respectively ( p = 0.0001). One-year survival for CMR and non-CMR patients was 93% and 47%, respectively and 2 years survival was 62% and 30%, respectively. Excluding PMD patients, non-CMR patients had higher rates of local failure (HR 2.15, p = 0.009) and distant metastasis (HR 2.05, p = 0.041) than CMR patients. By last follow-up, 20 of 40 CR patients (50%) had PMD, with local failure ( n = 8), distant metastasis ( n = 2) or both ( n = 10). Conclusions: Attainment of CMR after radical RT/chemoRT for NSCLC bestows superior freedom from local and distant relapse; late local relapse is common.

A workshop, sponsored by the Rockefellar Foundation, was held between 9 to 16 July, 2003 to devise strategies to reduce mortality and improve quality of life of long-term survivors of Hodgkin's disease. Participants were selected for their clinical and research background on late effects after Hodgkin's disease therapy. Experts from both developed and developing nations were represented in the workshop, and efforts were made to ensure that the proposed strategies would be globally applicable whenever possible. The types of late complications, magnitude of the problem, contributing risk factors, methodology to assess the risk, and challenges faced by developing countries were presented. The main areas of late effects of Hodgkin's disease discussed were as follows: second malignancy, cardiac disease, infection, pulmonary dysfunction, endocrine abnormalities, and quality of life. This report summarizes the findings of the workshop, recommendations, and proposed research priorities in each of the above areas.

We conjecture that when the uncertainty of scheduling information increases, one should change from deterministic, through robust to, finally, online scheduling techniques. Previously, extensive mathematical investigations have been carried out on the stability of a deterministic schedule for uncertain operation processing times. In this paper, we will use an empirical approach and an entropy measure to justify the transition between deterministic, robust and online scheduling. The use of an entropy measure in our context can be perceived, in a broader sense, as a pro-active approach to deal with changes in the level of information uncertainty and relative importance of each term in the total schedule execution cost. The level of information uncertainty may change due to the performance deterioration of processors (machines or human) and the replacement of old machines with new ones; and the changes in relative importance of cost elements may be due to changes in shop floor priorities and pressure from partners in the supply chain network. One can decide upon the scheduling strategies to be employed based on the latest entropy value of the information considered and the relative importance of each cost term.

Background: Solitary bone plasmacytoma (SBP) is a rare tumor for which the standard treatment remains local radiotherapy (RT). While this results in high rates of local control, the majority of patients ultimately develop multiple myeloma (MM). Here we present a 20-year multi-institutional review of our experience in an attempt to better understand the natural history of SBP and to identify possible prognostic factors. Methods: A total of 44 patients were identified. The inclusion criteria were the presence of a solitary bone lesion with histologic confirmation of plasma cells on biopsy, a normal bone marrow aspiration and trephine (

Background: Solitary extramedullary plasmacytoma (SEP) is a rare tumour for which the standard treatment remains local radiotherapy (RT). We present a study of a multi-institutional experience, between 1980 and 1999, in an attempt to better understand the natural history of SEP and to identify possible prognostic factors. Methods: The records at Radiation Oncology Victoria and Peter MacCallum Cancer Centre, Melbourne, were used for the identification of patients. The inclusion criteria were as follows: (i) histological confirmation of clonal plasma cells involving a single extramedullary site with or without lymph node involvement; (ii) no histological evidence of bone marrow involvement; (iii) no evidence of distant bone lesion on radiographic skeletal survey (bone erosions adjacent to the primary thought to be due to contiguous involvement were permitted) and (iv) no anaemia, hypercalcaemia or renal impairment due to plasma cell dyscrasia. Results: A total of 16 patients was identified, with a median follow up of 66 months (range 12–211 months). The head and neck region accounted for the majority of presentations (88%). Among all patients, a serum mono­clonal paraprotein was found in three patients and bone erosion was identified in seven patients. All patients received local RT, although two patients also received elective nodal irradiation (ENI). The median RT dose was 45 Gy (range 40–50.4 Gy). Local control was achieved in all patients (100%), however, regional recurrence outside the RT fields occurred in 2/16. Multiple myeloma (MM) developed in five patients, all within 5 years. The predicted 10-year myeloma free survival is 75% and 10-year overall survival is 54%. Conclusion: RT can achieve excellent local control of SEP. The rate of conversion to MM is 31%. Moderate dose RT of at least 40 Gy using limited radiation fields is recommended, although ENI should be considered if toxicity is not increased. (Intern Med J 2005; 35: 211–215)

We examine the problem of scheduling jobs, on a single processor to minimise the total earliness and tardiness costs about a common due date. Jobs belong to mutually exclusive families and a sequence independent setup task is required when processing switches from a job of one family to a job of another.We extend earlier results to obtain necessary optimal conditions for this problem. These are then used to generate a fast heuristic. Its performance is compared with a lowerbound, a greedy heuristic, a genetic algorithm and for small problems, the optimal solution.

This paper considers the deterministic problem of scheduling two-operation non-preemptable jobs on two identical semi-automatic machines. A single server is available to carry out the first (or setup) operation. The second operation is executed automatically, without the server. The general problem of makespan minimization is NP-hard in the strong sense. Two special cases which arise in practice, the equal processing times and regular equal setup times problems turn out to be closely linked to the restricted set partitioning problem. This link is used to show that they are NP-hard in the ordinary sense, and to construct a tight lower bound and two highly effective O(n log n) heuristics.

The optimal chemoradiation regimen for stage III non-small cell lung cancer (NSCLC) has not been determined. In this phase I/II study, the use of twice-weekly paclitaxel concomitant with weekly cisplatin and thoracic radiotherapy (RT) was evaluated. Patients with stage III NSCLC (without pleural effusion or cervical lymphadenopathy) were treated with thoracic RT (60 Gy in 30 fractions over 6 weeks) with concurrent weekly cisplatin 20 mg/m(2) and escalating doses of twice-weekly paclitaxel (starting dose of paclitaxel of 20 mg/m(2) increased in increments of 5 mg/m(2)) in successive cohorts of three to six patients until two or more patients experienced dose limiting toxicities (DLTs) at a particular dose level. All patients were planned to be given a further two cycles of consolidation chemotherapy consisting of paclitaxel 175 mg/m(2) and carboplatin AUC 5 after completion of RT. Twenty-five patients were enrolled in this study from two institutions. At a dose of paclitaxel 35 mg/m(2), two of four treated patients had DLTs (1 grade 3 oesophagitis and pulmonary toxicity; 1 grade 3 oesophagitis and infection). The recommended dose was therefore determined to be 30 mg/m(2) and a total of 15 patients were enrolled in an expanded cohort at this level. The overall response rate for all patients was 64% (95% CI: 43-82%). The estimated median survival was 23.6 months with an estimated 1-year and 2-year survival of 72 and 49%, respectively. Paclitaxel can be safely given twice-weekly at a dose of 30 mg/m(2) in combination with weekly cisplatin (20 mg/m(2)) and thoracic RT (60 Gy), and this regimen has significant activity in stage III NSCLC.

[18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) is useful in staging aggressive non-Hodgkin's lymphoma (NHL). However, its role in indolent NHL has not been established. This retrospective study assessed the sensitivity and clinical impact of PET findings in patients with indolent NHL. Patients with indolent NHL who underwent FDG-PET scanning between May 1997 and August 2001 were identified. Case records were reviewed for FDG-PET and conventional staging/restaging results and compared for concordance. Forty-seven patients were identified. Twelve staging FDG-PET scans and 37 restaging FDG-PET scans were obtained. The FDG-PET case sensitivity rate was 98%. Forty-two percent of staging FDG-PET scans were concordant with conventional staging, with the remaining patients exhibiting more extensive disease on PET. At progression, FDG-PET and conventional assessments were discordant in 46% of cases. Positron emission tomography findings downstaged disease in 30% of these patients and upstaged disease in 16%. Computed tomography (CT) and FDG-PET identified 150 and 146 individual sites of disease, respectively. Among "definite" sites on structural imaging, 74% were also seen on PET. For equivocal lesions, only 19% were seen on both modalities. Clinical management was changed in 34% of patients as a result of FDG-PET findings. Of 22 discordant lesions in which true disease status could be evaluated, the PET findings were confirmed to be correct in 21 (95%; P < 0.0001). These findings demonstrate that FDG-PET has a high sensitivity for indolent NHL and often leads to alteration of disease staging and management. This high accuracy of FDG-PET in assessing discordant lesions suggests a greater diagnostic utility compared with CT.

The prognostic significance of extracranial distant metastasis detected by positron emission tomography (PET) was investigated in patients with non-small cell lung cancer (NSCLC). Forty-two patients staged with 18F-fluorodeoxyglucose-PET-detected distant metastasis before planned surgery (n = 7) or radical radiotherapy (RT)/chemoradiotherapy (n = 35) for NSCLC were identified from a prospective database. The influence of metastasis number and other prognostic factors was investigated using Cox's regression analysis. Treatment after PET included surgery (n = 2), radical RT (n = 5), palliative RT (n = 25), chemotherapy (n = 8) or supportive care (n = 2). All but 4 patients had died by the last follow-up. Median survival was 9 months overall, 12 months for 27 patients with single PET-detected metastasis and 5 months for 15 patients with > 1 metastasis (p = 0.009). It was found that the Eastern Cooperative Oncology Group performance status (p = 0.027) but not pre-PET stage, weight loss or metastasis site correlated with survival. PET-detected metastatic tumor burden appeared to influence survival and should be evaluated as a prognostic factor in NSCLC.

Purpose: To examine the interclinician variation in the definition of gross tumor volume (GTV) in patients undergoing radiotherapy for non-small-cell lung cancer (NSCLC), develop methods to minimize this variation, and test these methods. Methods and Materials: The radiotherapy planning computed tomography (CT) scans of 6 consecutive patients with NSCLC in which the radiologist was able to define and outline the GTV were used. Six oncologists independently contoured the tumors with the radiologist's markings as a guide using a three-dimensional treatment planning system. Separate contours were prepared using only mediastinal window settings and using both mediastinal and lung window settings. The volumes were calculated using the planning system software (series 1). Factors that resulted in interclinician variation were determined, and, after a 3-year interval, 5 of the 6 clinicians redefined the GTVs using a revised protocol aimed at minimizing variation (series 2). Results: For series 1, the interclinician variation in the measurement of volumes ranged from 5%, in the most tightly measured tumor, to 42%, in the most variable, but was, on average, 20%. Statistically significant differences were noted among the clinicians ( p = 0.002), that is, some clinicians tended to record relatively small and some relatively large volumes. The reasons for the variation among the oncologists included a tendency to include regions with a low probability of containing tumor, as if the oncologist were contouring a target volume; inclusion of adjacent atelectasis (ignoring the radiologist's outline); and variable treatment of spicules. When the exercise was repeated using the revised protocol (series 2), the degree of interclinician variation was reduced, with a range of 7–22% (average 13%). In series 2, the differences among the clinicians were not statistically significant ( p = 0.25). Conclusion: Despite major radiologic input, significant variation occurred in the delineation of the three-dimensional GTVs of NSCLC among oncologists. Standardization of the approach with guidelines resulted in a reduction in this variation.

Purpose To compare fluorine-18 fluorodeoxyglucose positron emission tomography (PET) and gallium scanning with each other and with conventional staging, for patients with Hodgkin's disease or non-Hodgkin's lymphoma. Subjects and methods Fifty patients had PET, gallium scanning, and conventional staging of newly diagnosed or progressive Hodgkin's disease or non-Hodgkin's lymphoma. Disease sites, stage, and treatment plans were assessed retrospectively. Results Positron emission tomography and gallium scanning each upstaged 14% of patients (n = 7). Management was altered by PET in 9 cases (18%) and by gallium scanning in 7 (14%, P = 0.6). Disease was evident in 117 sites in 42 patients. The case positivity rate for conventional assessment was 90%; for PET, 95%; for gallium scanning, 88%; for conventional assessment plus PET, 100%; and for conventional assessment plus gallium scanning, 98%. Site positivity rates for conventional assessment were 68%; for PET, 82%; for gallium scanning, 69% (conventional vs. PET, P = 0.01; conventional vs. gallium scanning, P = 0.9; PET vs. gallium scanning, P = 0.01); for conventional assessment plus PET, 96%; and for conventional assessment plus gallium scanning, 94%. Positron emission tomography and gallium scanning were entirely concordant in 31 patients; in the other 19 patients, PET identified 25 sites missed by gallium scanning, whereas gallium scanning identified 10 sites missed by PET. Conclusion In this retrospective study, PET demonstrated a higher site positivity rate than did gallium scanning, with similar case positivity rates. These data support the use of PET in place of gallium scanning for the staging of patients with Hodgkin's disease or non-Hodgkin's lymphoma.

This paper considers the problem of scheduling two identical parallel machines with a single server which is required to carry out the job setups. Job processing can then be carried out in parallel. The objective is to minimise maximum completion time, that is makespan. The problem is NP-complete in the strong sense. An integer program formulation is presented. Two special cases: short processing times and equal length jobs are solved. Two simple but effective O(n log n) heuristics for the general case are given and their performance is tested.