Search

Rationale: The objective was to assess the cost-effectiveness of staging positron emission tomography/computed tomography (PET/CT) in early-stage follicular lymphoma from the Canadian health care system perspective. Methods: The study population was FL patients staged as early-stage using conventional CT imaging and planned for curative-intent radiation therapy (RT). A decision analytic model simulated the management after adding a staging PET/CT vs. using staging CT alone. In the no-PET/CT strategy, all patients proceeded to curative-intent RT as planned. In the PET/CT strategy, PET/CT information could result in an increased RT volume, switching to a non-curative approach, or no change in RT treatment as planned. Subsequent disease course was described using a state-transition cohort model over a 30-year time horizon. Diagnostic characteristics, probabilities, utilities and costs were derived from the literature. Baseline analysis was performed using quality-adjusted life years (QALYs), costs (2019 Canadian dollars, CAD$) and the incremental cost-effectiveness ratio. Deterministic sensitivity analyses were conducted, evaluating net monetary benefit at a willingness-to-pay threshold of $100,000/QALY. Probabilistic sensitivity analysis using 10,000 simulations was performed. Costs and QALYs were discounted at a rate of 1.5%. Results: In the reference case scenario, staging PET/CT was the dominant strategy, resulting in an average lifetime cost saving of $3,165 and a gain of 0.32 QALYs. In deterministic sensitivity analyses, the PET/CT strategy remained the preferred strategy for all scenarios supported by available data. In probabilistic sensitivity analysis, the PET/CT strategy was strongly dominant in 77% of simulations (i.e., reduced cost and increased QALYs), and was cost-effective in 89% of simulations (i.e., either cost-saving or with an incremental cost-effectiveness ratio below $100,000/QALY). Conclusion: Our analysis shows that the use of PET/CT to stage early-stage FL patients reduces cost and improves QALYs. Patients with early-stage FL should undergo PET/CT prior to curative-intent RT.

Background This Phase 2 multicentre trial in localised non-gastric marginal zone lymphoma (MZL) evaluated the effectiveness and safety of radiotherapy and documented markers of autoimmunity and Helicobacter pylori infection. Patients and methods Eligible patients had Stages I and II or paired-organ, non-gastric MZL. Bone marrow evaluation, autoantibody panel, and H. pylori evaluation were mandatory. Involved-field or involved-site radiotherapy was delivered to 24–30.6 Gy. Detected H. pylori infections underwent eradication. Results Between 2006 and 2014, six centres enrolled 70 patients, and 68 commenced treatment. The median age was 59 (range: 23–84) years, and 31 (46%) were male. Overall, 55 patients had Stage I disease, nine patients had Stage II disease, and four patients had paired organ–confined disease. Involved extranodal sites with three or more cases were orbital (n = 18), conjunctiva (n = 13), lacrimal (n = 8), skin (n = 8), salivary (n = 7), and muscle (n = 4). Eight patients had primary nodal MZL. At the median follow-up of 5 years (range 0.7–9.4), progression-free survival and overall survival were 79% and 95%, respectively. One lymphoma-related death and two in-field failures (after 25 and 30 Gy, respectively) occurred. Distant relapse sites were skin (n = 2), lymph nodes (n = 2), duodenum, stomach, muscle, and conjunctiva (1 each). No paired-organ MZL relapsed. Apart from cataracts (n = 18), only three treatment-related late grade ≥3 adverse events occurred. Autoantibodies or autoimmune events were detected in 26 of 68 patients (38%). H. pylori infection was detected in 15 of 63 patients (24%) tested. Neither autoimmunity nor H. pylori was detected in 27 of 68 patients (40%). Conclusions Radiotherapy was a potentially curative treatment with low toxicity in localised non-gastric MZL. Autoimmunity, H. pylori infection or both were detected in 60% of patients.

PURPOSE: Patients with abscopal regressions of lymphoma after palliative involved-site radiation therapy (ISRT), detected on sequential 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), were identified by audit. A retrospective analysis was subsequently conducted to estimate the frequency of abscopal regression in follicular lymphoma (FL). METHODS AND MATERIALS: Potential cases were identified at multidisciplinary lymphoma meetings and fulfilled these criteria: (1) palliative ISRT given for histologically confirmed lymphoma, (2) >2 lesions visualized on FDG-PET, (3) >1 unirradiated lesion(s) outside ISRT volume, (4) no systemic therapy delivered

Total body irradiation (TBI) is an important treatment modality for the preparation of patients for bone marrow transplants. It is technically challenging and the actual delivery may vary from clinic to clinic. Knowledge of the pattern of practice may be helpful for clinics to determine future practice. We carried out an email survey from April to September 2019 sending 48 TBI related questions to all radiotherapy clinics in Australia and New Zealand via the Australasian College of Physical Scientists in Medicine email distribution list. Centres not performing TBI were not expected to complete the survey and centres that had participated in a previous survey, or that were known to perform the treatment, were followed up if no response was received. Of a total of approximately 70 centres, 14 clinics responded to the survey. The vast majority of clinics use conventional lateral and/or anterior-posterior beams at extended SSD for TBI treatment delivery. However, treatment planning, ancillary equipment (used for immobilisation/modulation), beam energy and prescribed lung doses vary considerably-with some clinics delivering the prescription dose to the lungs and some aiming to deliver a lung dose which is lower than the prescription dose. Only one clinic reported using an advanced delivery technique with modulated arcs at extended SSD. Centres either said they had no access to outcome data or did not answer this question. Compared with an earlier survey from 2005, 3 clinics have lowered their linac dose rate and 7 are the same or similar. The TBI practice in Australia and New Zealand remains varied, with considerable differences in treatment planning, beam energy, accepted lung doses and delivered dose rates.

The International Lymphoma Radiation Oncology Group (ILROG) guidelines for using radiation therapy (RT) in hematological malignancies are widely used in many countries. The emergency situation created by the COVID-19 pandemic may result in limitations of treatment resources. Furthermore, in recognition of the need to also reduce the exposure of patients and staff to potential infection with COVID-19, the ILROG task force has made recommendations for alternative radiation treatment schemes. The emphasis is on maintaining clinical efficacy and safety by increasing the dose per fraction while reducing the number of daily treatments. The guidance is informed by adhering to acceptable radiobiological parameters and clinical tolerability. The options for delaying or omitting RT in some hematological categories are also discussed.

FDG-PET scanning has a central role in lymphoma staging and response assessment. There is a growing body of evidence that PET response assessment during and after initial systemic therapy can provide useful prognostic information, and PET response has an evolving role in guiding patient care. This review provides a perspective on the role of PET response assessment for individualised management of patients with the most common aggressive lymphomas, Hodgkin lymphoma and diffuse large B-cell lymphoma.

IntroductionLow muscle mass and low muscle attenuation (radiodensity), reflecting increased muscle adiposity, are prevalent muscle abnormalities in people with lung cancer receiving curative intent chemoradiation therapy (CRT) or radiation therapy (RT). Currently, there is a limited understanding of the magnitude, determinants and clinical significance of these muscle abnormalities in the lung cancer CRT/RT population. The primary objective of this study is to identify the predictors of muscle abnormalities (low muscle mass and muscle attenuation) and their depletion over time in people with lung cancer receiving CRT/RT. Secondary objectives are to assess the magnitude of change in these parameters and their association with health-related quality of life, treatment completion, toxicities and survival.Methods and analysisPatients diagnosed with lung cancer and planned for treatment with CRT/RT are invited to participate in this prospective observational study, with a target of 120 participants. The impact and predictors of muscle abnormalities (assessed via CT at the third lumbar vertebra) prior to and 2 months post CRT/RT on the severity of treatment toxicities, treatment completion and survival will be assessed by examining the following variables: demographic and clinical factors, weight loss, malnutrition, muscle strength, physical performance, energy and protein intake, physical activity and sedentary time, risk of sarcopenia (Strength, Assistance in walking, Rise from a chair, Climb stairs, Falls history (SARC-F) score alone and with calf-circumference) and systemic inflammation. A sample of purposively selected participants with muscle abnormalities will be invited to take part in semistructured interviews to understand their ability to cope with treatment and explore preference for treatment strategies focused on nutrition and exercise.Ethics and disseminationThe PREDICT study received ethics approval from the Human Research Ethics Committee at Peter MacCallum Cancer Centre (HREC/53147/PMCC-2019) and Deakin University (2019-320). Findings will be disseminated through peer review publications and conference presentations.

Radiotherapy (RT) can be curative in patients with localized follicular lymphoma (FL), with historical series showing a 10-year disease-free survival of 40 to 50%. As 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography with computerized tomography (PET-CT) upstages 10 to 60% of patients compared to CT, we sought to evaluate outcomes in patients staged by PET-CT, to determine if more accurate staging leads to better patient selection and results. We conducted a multicenter retrospective study under the direction of the International Lymphoma Radiation Oncology Group (ILROG). Inclusion criteria were: RT alone for untreated stage I to II FL (grade 1-3A) with dose equivalent ≥24 Gy, staged by PET-CT, age ≥18 years, and follow-up ≥3 months. End points were freedom from progression (FFP), local control, and overall survival (OS). A total of 512 patients treated between 2000 and 2017 at 16 centers were eligible for analysis; median age was 58 years (range, 20-90); 410 patients (80.1%) had stage I disease; median RT dose was 30 Gy (24-52); and median follow-up was 52 months (3.2-174.6). Five-year FFP and OS were 68.9% and 96%. For stage I, FFP was 74.1% vs 49.1% for stage II (P < .0001). Eight patients relapsed in-field (1.6%). Four had marginal recurrences (0.8%) resulting in local control rate of 97.6%. On multivariable analysis, stage II (hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.44-3.10) and BCL2 expression (HR, 1.62; 95% CI, 1.07-2.47) were significantly associated with less favorable FFP. Outcome after RT in PET-CT staged patients appears to be better than in earlier series, particularly in stage I disease, suggesting that the curative potential of RT for truly localized FL has been underestimated.

A multi-resolution approach to dynamic programming is presented, which reduces the computational effort of solving multistage optimization problems with long horizons and short decision intervals. The approach divides an optimization horizon into a series of subhorizons, discretized at different state space and temporal resolutions, enabling a reduced computational complexity compared to a single-resolution approach. The method is applied to optimizing the operation of a residential energy storage system, using real 1-min demand and rooftop PV generation data. The multi-resolution approach reduces the required computation time, allowing optimization to be rerun more frequently, increasing the robustness of the receding-horizon-control approach to forecast errors. In an empirical study, this increases the cost-saving offered by a 2 kWh behind-the-meter battery energy storage system by 120% on average, compared to an approach using a single fine-grained resolution.

Purpose/objective(s) Radiotherapy is curative for the majority of patients with IOAL. Some reports suggest inferior outcomes for bilateral IOAL, leading to uncertainty regarding optimal management for this presentation. This retrospective, international study evaluated long-term outcomes of bilateral IOAL treated with radiotherapy alone, with the current analysis limited to synchronous presentations (defined as ≤90 days between diagnoses). Materials/methods Ninety patients with bilateral synchronous IOAL were treated with radiotherapy to both orbits at 13 centers. Overall (OS), progression-free survival (PFS), freedom from local (FFLF) and freedom from distant (FFDF) failure were measured from the commencement of treatment of the second orbit. The study met local institutional review board requirements. Results The median age at diagnosis was 55 years (range 15-83), with 47% males. Histology was marginal zone lymphoma in 90% and disease was conjunctival in 65% of orbits. Sixty-three percent had bilateral conjunctival disease. The radiotherapy dose (per orbit) was 20-25.2 Gy for 46%, 27-30.6 Gy for 33%, 33-40 Gy for 8% and 13% had 4 Gy. Radiotherapy was given to the whole orbit for 62% of orbits, conjunctiva only for 29% and other partial orbit for 9%. Median follow-up was 6.6 years. The 10-year OS and PFS were 99% (95% CI: 92-100) and 73% (95% CI: 60-82), respectively. Ten-year FFLF and FFDF were 88% (95% CI: 78-94) and 83% (95% CI: 70-91), respectively. PFS was lower for the 33 patients with one or both orbits having non-conjunctival disease (HR 3.7 (1.4-9.3), P = 0.004). Three-year FFLP was 91% (95% CI: 81-95) for orbits receiving ≥ 20 Gy and 61% (95% CI: 27-84) after 4Gy (P Conclusion In this large, multicenter experience, patients with bilateral, synchronous IOAL treated with radiotherapy alone appeared to have outcomes comparable to historical series of unilateral disease. These results would suggest bilateral IOAL can be considered a localized process and support the use of curative intent radiotherapy in this setting.

The treatment of diffuse large B-cell lymphoma (DLBCL) has evolved considerably over recent decades. The incorporation of new agents into clinical practice has led to improved patient survival rate...

At diagnosis,1% of patients with non-small cell lung cancer (NSCLC) have synchronous solitary brain metastasis (SSBM). In prior cohorts without 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) staging, definitive treatment to intracranial and intrathoracic disease showed a 5-year overall survival (OS) of 11-21%. We investigated the long-term survival outcomes for patients with SSBM NSCLC, diagnosed in the FDG-PET/CT era and treated definitively with local therapies to both intracranial and intrathoracic sites of disease.This retrospective study assessed patients staged with FDG-PET/CT who received definitive lung and SSBM treatment from February 1999 to December 2017. A lung-molecular graded prognostic assessment (lung-molGPA) score was assigned for each patient using age, performance status score, and, where carried out, molecular status. Overall survival and progression-free survival (PFS) were calculated using Kaplan-Meier methods. Cox proportional hazard models determined OS and PFS prognostic factors.Forty-nine patients newly diagnosed with NSCLC and SSBM had a median age of 63 years (range 34-76). The median follow-up of all patients was 3.9 years. Thirty-three patients (67%) had ≥T2 disease, 23 (47%) had ≥N2. At 2 years, 45% of first failures were intracranial only (95% confidence interval 30-59). At 3 and 5 years, OS was 45% (95% confidence interval 32-63) and 30% (95% confidence interval 18-51), respectively. In ≥N1 disease, 5-year OS was 34% (95% confidence interval 18-63). The 3- and 5-year PFS was 8% (95% confidence interval 3-22) and 0%, respectively. Higher lung-molGPA was associated with longer OS (hazard ratio 0.26, 95% confidence interval 0.11-0.61, P = 0.002). Higher lung-molGPA (hazard ratio 0.33, 95% confidence interval 0.15-0.71, P = 0.005) and lower N-stage (hazard ratio 1.56, 95% confidence interval 1.13-2.15, P = 0.007) were associated with longer PFS.Definitive treatment of patients with NSCLC and SSBM staged with FDG-PET/CT can result in 5-year survivors, including those with ≥N1 disease.

Advanced-stage follicular lymphoma (FL) is generally considered incurable with conventional systemic therapies, but historic series describe long-term disease-free survival in stage III disease treated with wide-field radiation therapy (WFRT), encompassing all known disease sites. We report outcomes for patients staged with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and treated with CT-planned WFRT, given as either comprehensive lymphatic irradiation (CLI) or total nodal irradiation (TNI). This analysis of a prospective cohort includes PET-staged patients given curative-intent WFRT as a component of initial therapy, or as sole treatment for stage III FL. Thirty-three PET-staged patients with stage III FL received WFRT to 24&ndash, 30Gy between 1999 and 2017. Fifteen patients also received planned systemic therapy (containing rituximab in 11 cases) as part of their primary treatment. At 10 years, overall survival and freedom from progression (FFP) were 100% and 75%, respectively. None of the 11 rituximab-treated patients have relapsed. Nine relapses occurred, seven patients required treatment, and all responded to salvage therapies. A single death occurred at 16 years. The principal acute toxicity was transient hematologic, one patient had residual grade two toxicity at one year. With FDG-PET staging, most patients with stage III FL experience prolonged FFP after WFRT, especially when combined with rituximab.

Involved node radiation therapy for lymphoma was introduced with the aim of using the smallest effective treatment volume, individualized to the patient's disease distribution, to avoid the potentially unnecessary normal tissue exposure and toxicity risks associated with traditional involved field radiation therapy. The successful implementation of involved node radiation therapy requires optimal imaging and precise coregistration of baseline imaging with the radiation therapy planning computed tomography scan. Limitations of baseline imaging, changes in patient position, and anatomic changes after chemotherapy may make this difficult in routine practice. Involved site radiation therapy (ISRT) was introduced by the International Lymphoma Radiation Oncology Group as a slightly larger treated volume, intended to allow for commonly encountered uncertainties. In addition to imaging considerations, the optimal ISRT treatment volume also depends on disease histology, stage, nodal or extranodal location, and the type and efficacy of systemic therapy, which in turn influence the distribution of macroscopic and potential subclinical disease. This article presents a systematic overview of ISRT, updating key evidence and highlighting differences in the application of ISRT across the lymphoma clinical spectrum.

To evaluate the impact of positron emission tomography (PET) staging on overall survival (OS) and progression-free survival (PFS) in patients with early-stage (stages I and II) follicular lymphoma (ESFL) treated with radiation therapy alone. Eighty-five patients with ESFL treated with curative-intent radiation therapy (RT) between December 2000 and May 2011 were identified. Of those, 13 who had no PET staging and 25 who received additional systemic therapy were excluded from the analysis. Thus, we analyzed 47 patients with PET-staged ESFL treated with definitive radiation therapy alone (dose > 23Gy). Tumour features, pre-treatment computed tomography (CT) and PET stage, dose fractionation, and radiation therapy field extent were recorded. The Kaplan–Meier method was used to estimate the OS and PFS. Patterns of failure were assessed as cumulative incidences assuming competing risks. Median age was 57 years (range 24–83); 43% were females. Most were PET stage 1 (76.6%). Median maximum nodal diameter was 3 cm. Median pre-treatment lactate dehydrogenase (LDH) was 327.5 (range 123–607, upper normal limit = 220). Twenty-six patients (55.3%) had infra-diaphragmatic disease. All received 30–36Gy in 15–24 fractions, with 59.6% treated with involved-field radiation therapy (IFRT) techniques. There was no significant difference in PFS between CT stage I and stage II (HR 1.30 95% CI [0.25–6.72], p = 0.75) with a 5-year PFS of 77% and 78% respectively. However, stage I on PET staging had a significantly better PFS than stage II (HR 4.66 95% CI [1.15–18.8], p = 0.038), with 5-year PFS of 84% and 60% respectively. Ten patients had recurrent disease, with distant disease being the first site of failure in seven patients. Seven-year OS was 91% (95% CI 79–100) for the whole cohort. FDG-PET should be considered an essential element in the evaluation of patients with ESFL being considered for RT.

Energy storage systems have the potential to deliver value in multiple ways, and these must be traded off against one another. An operational strategy that aims to maximize the returned value of such a system can often be significantly improved with the use of forecasting — of demand, generation, and pricing — but consideration of battery degradation is important too. This paper proposes a stochastic dynamic programming approach to optimally operate an energy storage system across a receding horizon. The method operates an energy storage asset to deliver maximal lifetime value, by using available forecasts and by applying a multi-factor battery degradation model that takes into account operational impacts on system degradation. Applying the method to a dataset of a residential Australian customer base demonstrates that an optimally operated system returns a lifetime value which is 160% more, on average, than that of the same system operated using a set-point-based method applied in many settings today.

Cardiophrenic lymph nodes (CPLNs) are occasionally involved in Hodgkin lymphoma (HL). We characterized the incidence of CPLN involvement among 169 HL patients and evaluated outcomes after treatment with omission of the CPLN region from the involved-site radiation therapy (ISRT) field. Three types of RT fields were used: standard (S)-ISRT, reduced-dose (RD)-ISRT (lower dose to CPLNs, standard to other sites), or modified (M)-ISRT (omission of CPLNs). CPLNs were involved at diagnosis in 29 patients (17%). Of the 20 patients who received RT after complete response to chemotherapy, 4(20%) received S-ISRT, 8(40%) RD-ISRT, and 8(40%) M-ISRT. The four-year progression-free survival was 94.7%. One relapse occurred at a non-CPLN site after RD-ISRT. The mean heart dose and volume of the heart that received 25 Gy was higher for S-ISRT patients compared to M-ISRT (p = .043 and p = .025, respectively). Re-planning the M-ISRT cases as S-ISRT resulted in significant increase in cardiac doses.

Patients diagnosed with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) achieve excellent disease control and survival regardless of their initial treatment s...

Purpose/Objective(s) This phase 2 multicenter clinical trial evaluated the effectiveness and safety of radiotherapy in localized non-gastric marginal zone lymphoma (MZL) and assessed the prevalence of markers of autoimmunity and Helicobacter pylori (HP) infection in this population. It was designed to test the hypotheses that-long term local progression-free survival (PFS) would be > 80% and that death within 10 years would occur in Materials/Methods Eligibility required untreated stage I-II, or bilateral paired-organ confined (e.g., bilateral conjunctival), non-gastric MZL. CT scanning, bone marrow biopsy, autoantibody serology panel and HP evaluation by urease breath test or endoscopy were mandatory. Involved-field or involved-site, conventionally-fractionated radiotherapy was delivered to 30-30.6 Gy, except for orbital MZL which received 24-25 Gy. Patients with detected HP infections additionally received eradication therapy. Results Between 2006 and 2014, six centers enrolled 70 patients, 68 of whom commenced protocol treatment. Median age was 59 (range: 23-84) years and 31 (46%) were male. Stage was I n = 55, II n = 9 and paired-organ confined n = 4. Involved extranodal sites with ≥ 3 cases were orbital n = 18, conjunctiva n = 13, lacrimal n = 8, skin n = 8, salivary n = 7, muscle n = 3. Four patients had primary nodal MZL and 14 (21%) patients were PET-staged. With a median follow-up of 5 years (range 0.7–9.4), 5-year progression-free and overall survival rates were 79% and 95% respectively. One lymphoma-related death and 2 in-field failures (after 25 and 30 Gy respectively) occurred. Distant relapse sites were skin (n = 2), lymph nodes (n = 2) duodenum, stomach, skeletal muscle and conjunctiva (1 each). No patient with bilateral paired-organ MZL relapsed. Apart from cataracts (n = 18), 6 grade 3 late adverse events occurred (3 treatment-related). Two grade 4 late events (nephrotic syndrome and thrombosis) were treatment-unrelated. Autoantibodies or auto-immune events were detected in 26 of 68 (38%) patients. HP infection was detected (and treated) in 15 of 63 patients tested (24%). Neither autoimmunity nor HP was detected in 27/68 (40%) patients. Conclusion Radiotherapy was a highly-effective, potentially-curative treatment with low toxicity in localized non-gastric MZL. Autoimmunity, HP infection or both were detected in 60% of patients.

Purpose: We previously reported that ∼30% of patients with localized follicular lymphoma (FL)staged by 18F-fluorodeoxyglucose positron emission tomography-computed tomography receiving primary radiation therapy (RT)will relapse within 5 years. We sought to report outcomes for those who relapsed. Methods and Materials: We conducted a multicenter, retrospective study of patients aged ≥18 years who received RT ≥ 24 Gy for stage I to II, grade 1 to 3A FL, staged with 18F-fluorodeoxyglucose ( 18F-FDG)positron emission tomography-computed tomography. Observation was defined as >6 months without treatment from relapse. Overall survival (OS)and freedom from progression (FFP)were estimated with Kaplan-Meier analysis and univariable and multivariable analyses with Cox regression. Results: Of 512 patients with median follow-up of 52 months, 149 (29.1%)developed recurrent lymphoma at a median of 23 months (range, 1-143)after primary RT. Median follow-up was 33 months after relapse. Three-year OS was 91.4% after recurrence. OS was significantly worse for those with relapse ≤12 months from date of diagnosis versus all others—88.7% versus 97.6%, respectively (P =.01)—and remained significantly worse on multivariable analyses (follicular lymphoma international prognostic index–adjusted hazard ratio, 3.61; P =.009). Histology at relapse included 93 indolent (grade 1-3A), 3 FL grade 3B/not otherwise specified, and 18 diffuse large B-cell lymphoma; 35 patients did not undergo biopsy. Of those with follow-up ≥3 months who underwent biopsy (n = 74)or had presumed (n = 23)indolent recurrence, 58 patients (59.8%)were observed, 19 (19.6%)had systemic therapy, 16 (16.5%)had RT, and 4 (4.1%)had systemic therapy + RT. For patients with indolent recurrences that were observed, 3-year FFP or freedom from treatment was 56.6% (median, 48 months). For all patients with biopsied/presumed indolent recurrence receiving salvage treatment (n = 59, including 20 initially observed)3-year FFP was 73.9%. Conclusions: Prognosis for patients with relapsed FL after primary radiation therapy is excellent, supporting the role of primary radiation in the management of early stage disease. Patients with localized FL treated with primary RT who experience early relapse (

In the treatment of diffuse large B-cell lymphoma, a persistently positive [18F]fluorodeoxyglucose positron emission tomography (PET) scan typically carries a poor prognosis. In this prospective multi-center phase II study, we sought to establish whether treatment intensification with R-ICE (rituximab, ifosfamide, carboplatin, and etoposide) chemotherapy followed by 90Y-ibritumomab tiuxetan–BEAM (BCNU, etoposide, cytarabine, and melphalan) for high-risk diffuse large B-cell lymphoma patients who are positive on interim PET scan after 4 cycles of R-CHOP-14 (rituximab, cyclophosphamide, doxorubicin, and prednisone) can improve 2-year progression-free survival from a historically unfavorable rate of 40% to a rate of 65%. Patients received 4 cycles of R-CHOP-14, followed by a centrally-reviewed PET performed at day 17–20 of cycle 4 and assessed according to International Harmonisation Project criteria. Median age of the 151 evaluable patients was 57 years, with 79% stages 3–4, 54% bulk, and 54% International Prognostic Index 3–5. Among the 143 patients undergoing interim PET, 101 (71%) were PET-negative (96 of whom completed R-CHOP), 42 (29%) were PET-positive (32 of whom completed R-ICE and 90Y-ibritumomab tiuxetan-BEAM). At a median follow up of 35 months, the 2-year progression-free survival for PET-positive patients was 67%, a rate similar to that for PET-negative patients treated with R-CHOP-14 (74%, P=0.11); overall survival was 78% and 88% (P=0.11), respectively. In an exploratory analysis, progression-free and overall survival were markedly superior for PET-positive Deauville score 4 versus score 5 (P=0.0002 and P=0.001, respectively). Therefore, diffuse large B-cell lymphoma patients who are PET-positive after 4 cycles of R-CHOP-14 and who switched to R-ICE and 90Y-ibritumomab tiuxetan-BEAM achieved favorable survival outcomes similar to those for PET-negative R-CHOP-14-treated patients. Further studies are warranted to confirm these promising results. (Registered at: ACTRN12609001077257).

The economical operation of many distributed energy assets relies on effective on-line control, which in turn often requires forecasts to be made. To produce and evaluate forecasts, the error metric by which one measures forecast accuracy must be selected. A new method is presented which customizes a forecast error metric to a given on-line control problem instance, in order to improve the controller's performance. This method is applied to the real-time operation of a battery with the objective of minimizing the peak power drawn by an aggregation of customers over a billing period. In the empirical example considered, customizing the forecast error metric to each problem instance, improved performance by 45% on average, compared to a controller provided with a forecast of the same type, but trained to minimize mean-squared-error. Error metric customization is made possible by two newly proposed parametrized error metrics. The proposed method can be applied to any on-line optimization problem which requires a point forecast as an input, and which can be accurately simulated ahead of time. The method is likely to be most effective in applications where forecasting errors are quite high, as in these applications the choice of forecast error metric significantly affects the forecasts which are produced.

Malnutrition is prevalent in patients undergoing (chemo)radiotherapy (RT) for lung cancer. This pilot study tested the feasibility and acceptability of delivering an intensive nutrition intervention for lung cancer patients receiving RT. Twenty-four patients with lung cancer were randomized to receive the intervention which employed a care pathway to guide intensive dietary counseling from pretreatment until 6-wk posttreatment or usual care. Nutritional, fatigue, and functional outcomes were assessed using valid and reliable questionnaires before randomization, at the start and end of RT and 1- and 3-mo post-RT. Consent rate was 57% with an overall attrition of 37%. Subject compliance with the completion of study questionnaires was 100%. A clinically important mean difference indicated greater overall satisfaction with nutritional care in the intervention group (5.00, interquartile range [IQR] 4.50-5.00; 4.00, IQR 4.00-4.00). Clinically important differences favoring the intervention were observed for weight (3.0 kg; 95% confidence interval [CI] -0.8, 6.8), fat-free mass (0.6 kg; 95% CI -2.1, 3.3), physical well-being (2.1; 95% CI -2.3, 6.5), and functional well-being (5.1; 95% CI 1.6, 8.6), but all 95% CIs were wide and most included zero. Recruitment feasibility and acceptability of the intervention were demonstrated, which suggest larger trials using an intensive nutrition intervention would be achievable.

Introduction Where tolerated,high dose chemotherapy supported by autologous stem cell transplantation (ASCT) is the standard of care for patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL). Disease recurrence post-ASCT however is common and carries an extremely poor prognosis, highlighting the need for improved pre-transplant prognostic stratification. This study investigates the prognostic utility of the PET parameters total metabolic tumour volume (TMTV) and standardised uptake value (SUV)max in the peri-transplant setting. Methods 125 patients underwent ASCT for relapsed or refractory DLBCL between 1/1/2002 and 31/1/2017 at the Peter MacCallum Cancer Centre. All patients received multi-agent salvage immuno-chemotherapy before proceeding to ASCT. 58 patients were treated with peri-transplant radiotherapy, with indications including incomplete response post-salvage therapy, and bulky and/or localised disease. 122 patients had their treatment response assessed with PET. TMTV and SUVmax were measured at time of primary disease relapse/progression prior to salvage immuno-chemotherapy (pre-salvage PET) and post-salvage immuno-chemotherapy prior to ASCT (pre-ASCT PET). 93 patients had pre-salvage and pre-ASCT PETs available for TMTV and SUVmax measurement. Results Median follow up was 5.6 years. The 5-year progression free survival (PFS) and overall survival (OS) were 52% (95% CI: 42-60) and 65% (95% CI: 56-73). In patients demonstrating complete metabolic response (CMR) and non-CMR on pre-ASCT PET the 5-year PFS was 58% (95% CI: 44-70) and 44% (95% CI: 29-57) respectively. The 5-year OS with CMR and non-CMR on pre-ASCT PET was 73% (95% CI: 59-83) and 54% (95% CI: 39-67). TMTV and SUVmax were investigated as potential prognostic factors in the peri-transplant setting. In this patient group, pre-salvage TMTV and SUVmax were not found to be of prognostic significance. Pre-salvage TMTV and SUVmax PFS hazard ratios (HR)s were 1.06 per 100ml (95% CI:0.96-1.17; p = 0.27) and 1.00 (95% CI: 0.98-1.03; p = 0.78) respectively, and OS HRs were 1.10 per 100ml (95% CI: 0.86-1.18; p = 0.07) and 1.02 (95% CI: 0.96-1.04 p = 0.24). In contrast, pre-ASCT TMTV was a significant negative prognostic factor for both PFS (HR = 1.22 per 100ml; 95%CI: 1.10-1.37; p < 0.001) and OS (HR = 1.96 per 100ml; 95% CI: 1.38-2.79; p < 0.001). Pre-ASCT SUVmax similarly demonstrated a negative association with PFS (HR = 1.07; 95% CI: 1.04-1.10; p < 0.001) and OS (HR of 1.08 ; 95% CI: 1.04-1.11; p < 0.001). In addition to the TMTV and SUVmax absolute values, the relative change from pre-salvage to pre-ASCT PET was investigated for prognostic value. No significant association with PFS or OS was demonstrated for the relative change of either parameter. The relative change in TMTV had a HRs of 1.21 (95% CI: 0.54- 2.72; p = 0.65) and 1.15 (95% CI: 0.45-2.93; p = 0.77) for PFS and OS respectively, and relative change in SUVmax had a HRs of 1.30 (95% CI: 0.68- 2.50; p = 0.43) and 1.20 (CI 95% 0.57-2.54; p = 0.64) for PFS and OS. Conclusion As prognostic tools, pre-ASCT TMTV and SUVmax were both predictors for PFS and OS. In contrast, pre-salvage TMTV and SUVmax did not demonstrate an association with PFS or OS, reinforcing the prognostic significance of the pre-ASCT PET scan. The relative change in SUVmax and TMTV were similarly not associated with PFS and OS. These findings indicate that in the context of TMTV and SUVmax measurement, residual disease on pre-ASCT PET may be of greater predictive value than degree of response to salvage immuno-chemotherapy. While TMTV and SUVmax have primarily been studied in the context of first-line therapy for DLBCL, these results suggest a promising prognostic role for these PET parameters in the peri-transplant setting. Disclosures Seymour: AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Research Funding; F. Hoffmann-La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gilead: Consultancy; Nurix: Honoraria; Mei Pharma: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria. Dickinson:Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Merck Sharp & Dohme: Consultancy; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

The optimal management of early-stage diffuse large B-cell lymphoma (DLBCL) remains uncertain, in part due to challenges of interpreting early-stage DLBCL studies. While early-stage disease compris...

Background: Stereotactic ablative body radiotherapy (SABR) is widely used to treat inoperable stage 1 non-small-cell lung cancer (NSCLC), despite the absence of prospective evidence that this type of treatment improves local control or prolongs overall survival compared with standard radiotherapy. We aimed to compare the two treatment techniques. Methods: We did this multicentre, phase 3, randomised, controlled trial in 11 hospitals in Australia and three hospitals in New Zealand. Patients were eligible if they were aged 18 years or older, had biopsy-confirmed stage 1 (T1–T2aN0M0) NSCLC diagnosed on the basis of F-fluorodeoxyglucose PET, and were medically inoperable or had refused surgery. Patients had to have an Eastern Cooperative Oncology Group performance status of 0 or 1, and the tumour had to be peripherally located. Patients were randomly assigned after stratification for T stage and operability in a 2:1 ratio to SABR (54 Gy in three 18 Gy fractions, or 48 Gy in four 12 Gy fractions if the tumour was

Purpose The role of involved-field radiation therapy (IFRT) with autologous stem cell transplantation (ASCT) for lymphomas remains uncertain. Methods and Materials In this prospective, multicenter study, patients undergoing ASCT for relapsed/refractory lymphoma received peritransplant IFRT to disease sites identified at study registration (SR) (before salvage chemotherapy [SC]). Radiation dose was adapted to SC response. Survival, relapse rates/pattern, toxicity, and prognostic factors were evaluated. Results Forty-five patients were enrolled (23 with Hodgkin lymphoma, 22 with aggressive non-Hodgkin lymphoma). Three-year overall survival and cumulative incidence of posttransplant progression rates were 72% (95% confidence interval [CI], 59%-87%) and 42% (95% CI, 27%-57%), respectively. Stage (P = .03) and elevated lactate dehydrogenase (P = .05) were significant risk factors for disease progression on multivariable analysis. Three-year actuarial in-field, marginal, and distant progression rates were 7% (95% CI, 0%-15%), 9% (95% CI, 0%-18%), and 36% (95% CI, 21%-51%), respectively. Progression occurred in 8 of 30 patients with all sites irradiated and in 13 of 15 patients without all sites irradiated. There were 117 disease sites at SR and 64 post-ASCT progression sites, of which 15 were involved at SR and 12 only at initial diagnosis. Posttransplant relapse occurred in 3 of 83 irradiated and 12 of 34 unirradiated involved sites. Of 28 sites in complete response to SC on computed tomography, there was no relapse in any of the 21 irradiated sites and in 1 of 7 unirradiated sites. Of 72 sites in complete response on positron emission tomography, relapse occurred in 1 of 50 irradiated and 10 of 22 unirradiated sites. No grade 4 nonhematologic radiation therapy toxicities were observed. Conclusions IFRT was well tolerated and associated with a low rate of in-field progression. Progression rates were lower for patients with all disease sites irradiated. Response to SC on both computed tomography and positron emission tomography warrants further study to select sites for IFRT.

Radiotherapy (RT) can be curative in patients with localized follicular lymphoma (FL), with historical series showing a 10-year disease-free survival of 40 to 50%. As

Approximately 30% to 40% of patients with diffuse large B-cell lymphoma (DLBCL) will have either primary refractory disease or relapse after chemotherapy. In transplant-eligible patients, those with disease sensitive to salvage chemotherapy will significantly benefit from high-dose therapy with autologous stem cell transplantation. The rationale for considering radiation therapy (RT) for selected patients with relapsed/refractory DLBCL as a part of the salvage program is based on data regarding the patterns of relapse and retrospective series showing improved local control and clinical outcomes for patients who received peritransplant RT. In transplant-ineligible patients, RT can provide effective palliation and, in selected cases, be administered with curative intent if the relapsed/refractory disease is localized. We have reviewed the indications for RT in the setting of relapsed/refractory DLBCL and provided recommendations regarding the optimal timing of RT, dose fractionation scheme, and treatment volume in the context of specific case scenarios.

Relapsed and refractory Hodgkin lymphoma (HL) challenges clinicians to devise treatment strategies that are effective and safe. This problem is particularly prominent in an era when de-escalation trials are designed to minimize therapeutic toxicities in both early- and advanced-stage disease. Radiation therapy is the single most effective treatment modality for HL, and its integration into salvage regimens, or its independent use in select patients, must be understood to maximize our success in treating these patients. The complexity of treating relapsed or refractory HL derives from the spectrum of primary treatment approaches currently in use that creates heterogeneity in both treatment exposure and the potential toxicities of salvage therapy. Patients can have relapsed or refractory disease after limited or aggressive primary therapy (with or without radiation therapy), at early or delayed time points, with limited or extensive disease volumes, and with varying degrees of residual morbidity from primary therapy. Their response to salvage systemic therapy can be partial or complete, and the use of consolidative stem cell transplantation is variably applied. New biologics and immunotherapeutic approaches have broadened but also complicated salvage treatment approaches. Through all of this, radiation therapy remains an integral component of treatment for many patients, but it must be used effectively and judiciously. The purpose of this review is to describe the different treatment scenarios and provide guidance for radiation dose, volume, and timing in patients with relapsed or refractory HL.

Background Mantle cell lymphoma (MCL) rarely presents as early-stage disease, but clinical observations suggest that patients who present with early-stage disease may have better outcomes than those with advanced-stage disease. Patients and methods In this 13-institution study, we examined outcomes among 179 patients with early-stage (stage I or II) MCL in an attempt to identify prognostic factors that influence treatment selection and outcome. Variables examined included clinical characteristics, treatment modality, response to therapy, sites of failure, and survival. Results Patients were predominantly male (78%) with head and neck being the most common presenting sites (75%). Most failures occurred outside the original disease site (79%). Although the administration of radiation therapy, either alone or with chemotherapy, reduced the risk of local failure, it did not translate into an improved freedom from progression or overall survival (OS). The treatment outcomes were independent of treatment modality. The 10-year OS for patients treated with chemotherapy alone, chemo-radiation therapy and radiation therapy alone were 69%, 62%, and 74% (P = 0.79), and the 10-year freedom from progression were 46%, 43%, and 31% (P = 0.64), respectively. Conclusion Given the excellent OS rates regardless of initial therapy in patients with early-stage MCL, de-intensified therapy to limit treatment-related toxicity is a reasonable approach.

Much research is being conducted into the potential value of residential energy storage. The temporal resolution of the analyses carried out in these studies is typically driven by the available data, which is often only at 30-minute or 1-hour intervals. This study uses higher temporal resolution data to examine the effect of input time-series resolution on the value determined for residential storage. In the case study considered, an analysis carried out at a 30-minute interval underestimates the cost-saving delivered by 5kWh of residential energy storage by 17% on average, compared to the same battery analyzed at a 1-minute interval. The sensitivity of storage value to temporal resolution is found to vary significantly from one customer to the next. A method for improving estimates of the realtime value of energy storage using coarser time-series data is introduced. Finally the impact of temporal resolution on storage technology selection is also evaluated.

There are limited data regarding the role of (18)F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG PET-CT) scanning in primary mediastinal B-cell lymphoma (PMBL). We analyzed 28 patients with PMBL treated with chemotherapy, of whom 25 (89%) also received rituximab and 17 (61%) radiotherapy. PET-CT scans were interpreted using visual analysis and a 5-point scale. After a median follow-up of 2.6 years, four patients relapsed and two died. The 2-year progression-free survival and overall survival were 86% and 94%. PET-CT has excellent negative predictive value (interim, 86-87%; end of treatment, 95%) but limited positive predictive value due to the high frequency of positive scans. Several patients with persistent metabolically active masses underwent biopsies, which showed necrosis but no lymphoma. Thus a negative PET-CT is an excellent predictor of subsequent outcome. However, residual metabolically active masses after treatment should be biopsied to confirm viable lymphoma prior to salvage therapy.