Belinda Campbell - Academia.edu (original) (raw)

Papers by Belinda Campbell

Internal medicine journal, Jun 1, 2024

Radiotherapy and Oncology

$Research paper thumbnail of Pushing the CART to the Finish Line: Integrating Radiation Therapy Into Chimeric Antigen Receptor T-Cell Therapy Programs to Improve Outcomes for Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma$

International journal of radiation oncology, biology, physics, Apr 1, 2024

more common mechanism for malignant SVCO. Non-small cell and small cell lung cancers constitute t... more more common mechanism for malignant SVCO. Non-small cell and small cell lung cancers constitute the more common histologies, with metastatic mediastinal lymphadenopathy or direct mediastinal invasion causing the SVCO. Radiotherapy is the traditional treatment of choice for patients with SVCO. For patients with severe symptoms, treatment of SVCO constitutes a medical emergency and requires urgent treatment with endovascular stenting to restore patency and produce rapid relief of potentially lifethreatening symptoms.

JACC: Cardiooncology, Jun 1, 2020

BACKGROUND Cancer treatment can lead to left ventricular (LV) dysfunction in female cancer surviv... more BACKGROUND Cancer treatment can lead to left ventricular (LV) dysfunction in female cancer survivors of reproductive age, and pregnancy-related hemodynamic stress may result in LV dysfunction or heart failure (HF). OBJECTIVES The authors performed a systematic review and meta-analysis to determine the incidence of LV systolic dysfunction or HF during or soon after pregnancy in cancer survivors and evaluated the impact of history of cancer therapeutics-related cardiac dysfunction (CTRCD). METHODS We systematically searched electronic databases (MEDLINE and EMBASE) from inception to January 2020 to identify cohort studies that examined cardiac disease in pregnant cancer survivors. Meta-analysis was performed using the inverse-variance fixed effects method. Potential sources of heterogeneity were explored using subgroup analyses and meta-regression. RESULTS Of 13,782 identified articles, 6 studies consisting of 2,016 pregnancies, predominantly in childhood cancer survivors, were included. Overall, there were 33 cardiac events. The total weighted incidence of LV dysfunction or HF with pregnancy was 1.7% (95% confidence interval [CI]: 0.9% to 2.7%) overall; 28.4% (95% CI: 14.6% to 43.9%) in those with a history of CTRCD and 0.24% (95% CI: 0% to 0.81%) in those without, translating into an odds ratio of 47.4 (95% CI: 17.9 to 125.8). Interstudy heterogeneity was low (I 2 ¼ 17.5%). Metaregression did not reveal significant sources of heterogeneity. CONCLUSIONS The incidence of LV dysfunction or HF during pregnancy in cancer survivors was low. Although risk estimates are limited by the small number of events, women with a history of CTRCD compared to those without had a 47.4-fold higher odds of experiencing pregnancy-related LV dysfunction or HF.

Journal of Clinical Oncology, Jun 1, 2022

Background: Follicular lymphoma (FL) is the commonest indolent lymphoma, comprising 20% of non-Ho... more Background: Follicular lymphoma (FL) is the commonest indolent lymphoma, comprising 20% of non-Hodgkin Lymphoma, with approximately 80% of patients (pts) requiring therapy. At present, advanced stage is incurable; most pts require >1 treatment. Overall response rates (ORR) to standard chemoimmunotherapy (bendamustine or CHOP with rituximab or obinutuzumab) approximate 85% with considerable toxicity (grade 3-5 in 69-75%) (Hiddemann 2018). With the FL population predominantly >65 years, 10-year median survival and need for further therapy, efficacious treatments with low toxicity are desirable. PD1/PDL1 axis inhibitors are active in FL. A phase I study of obinutuzumab (O) + atezolizumab (A) induced 57% ORR in pts with rituximab-refractory FL (Palomba 2017). Our phase II '1 st FLOR' study, combining nivolumab + rituximab in treatment naïve FL yielded 92% ORR, (54% Complete Response, CR). Toxicity profiles compared favourably with conventional chemotherapy: 41% grade 3-5 events (Hawkes 2021). FL is sensitive to low dose radiotherapy (RT), with abscopal effects reported, and potential to improve treatment efficacy with minimal additional toxicity when combined with PD1/PDL1 inhibitors (Sharabi 2015). This investigator initiated, multicentre single-arm phase II PET-adapted trial aims to assess the response of O + A +/-RT for treatment-naïve FL, reducing treatment-related toxicity using a chemotherapy-free, multi-modality, synergistic regimen. Methods: Eligible pts are >18 years, ECOG 0-2 with untreated, biopsy proven, grade 1-3A stage II-IV FL. Exclusions are significant compressive symptoms, autoimmune disease, pneumonitis and treatment urgency. All pts receive 6 cycles (q21 days) of O 1000mg + A 1200mg (plus O given on days 8 & 15 of cycle 1). Interim PET-CT is performed post cycle 2. Pts with less than CR will undergo RT (4Gy) to residual disease after cycle 3. At end of induction, responding patients will receive maintenance O (up to 12 cycles, 1000mg Q8W). Pts with significant progression will be taken off study. Total follow-up is 2 years post treatment. Primary endpoint is CR rate following 6 x O&A +/-RT. Secondary endpoints include ORR, PFS, OS and adverse events. PET centres are ARTnet accredited with central analysis. An extensive exploratory biomarker substudy is planned. Sample size is 46 according to a Simon's 2-stage design. If ≥5 positive responses (CR +/-PR) without prohibitive toxicity are seen in the first 15 pts, 31 further pts will be recruited.The trial has currently enrolled 7 pts from 4 Australian sites. Clinical trial information: NCT04962126

International Journal of Radiation Oncology Biology Physics, Nov 1, 2021

American Journal of Clinical Oncology, Aug 1, 2006

A 13-year-old girl presented with a painless swelling in her right forearm. Incisional biopsy rev... more A 13-year-old girl presented with a painless swelling in her right forearm. Incisional biopsy revealed alveolar softpart sarcoma. Workup for metastatic disease was negative. Neoadjuvant cisplatin/doxorubicin chemotherapy was delivered with limited response. Radical resection of the extensor compartment of the right forearm achieved clear surgical margins, with reconstitution of the tendons from the flexor compartment. Postoperative therapy consisted of a single course of vincristine, cyclophosphamide, and actinomycin D, followed by radiotherapy, 60 Gy in 30 fractions over 6 weeks, with a decreased field size after 50 Gy. Follow-up was unremarkable over a 6-year period, until radiologic surveillance of the chest revealed an asymptomatic, pulmonary lesion in the medial segment of the right middle lobe. The lesion was resected and confirmed histopathologically as metastatic sarcoma. Follow-up included 3 monthly chest radiographs, which remained unchanged for a further 7 years. At the age of 26, the patient underwent screening for late effects of her previous therapy, including cardiac assessment. Electrocardiograph was normal but transthoracic echocardiogram revealed an unexpected intraventricular mass. Transesophageal echocardiogram confirmed a 3.5 2.2-cm mass within the basal inferior wall of the left ventricle, with no associated motion abnormality of the wall. Further imaging of the thorax revealed the same cardiac mass on CT (Fig. 1), plus a 1.5-cm pulmonary nodule in the left anterolateral costophrenic angle. FDG-PET scanning did not reveal any uptake in the thorax or the primary site; however, small malignant deposits could not be excluded and a cardiac metastasis may have been masked by normal FDG uptake by the myocardium. Excisional biopsy of the pulmonary lesion confirmed metastatic alveolar soft-part sarcoma (Fig. 2). The cardiac lesion was unresectable, and due to its asymptomatic nature, no further therapy was administered. Fourteen months later, the then 28-year-old woman developed headache, vomiting, and visual disturbance. Cerebral MRI revealed 18 lesions in bilateral hemispheres, consistent with metastases. Palliative whole-brain radiotherapy was delivered to 30 Gy in 10 fractions, over 2 weeks, via opposing lateral beams. However, she developed symptomatic progressive intracerebral disease, confirmed on repeat MRI. She was managed supportively until her death 4 months later. The cardiac lesion remained asymptomatic throughout. Alveolar soft-part sarcoma is an indolent disease but is associated with overall poor outcome. Metastases to lung and brain are common, are often asymptomatic, and may be detected after long disease-free intervals. Long-term fol-

Journal of Clinical Oncology, May 20, 2010

ABSTRACT Background The established treatment of limited-stage follicular lymphoma is radiotherap... more ABSTRACT Background The established treatment of limited-stage follicular lymphoma is radiotherapy (RT). There is an inherent risk of transformation of follicular lymphoma to aggressive lymphoma; however, the frequency and impact on the outcome are unknown in limited-stage patients.Materials and methodsWe identified 237 patients with limited-stage follicular lymphoma treated with curative intent RT. Cases were reviewed to determine the frequency of transformation and subsequent survival.ResultsWith a median follow-up of 7.4 years, the 10-year risk of transformation was 18.5%. With a median follow-up after transformation of 4.7 years, the 3-year post-transformation progression-free survival (PFS) and overall survival (OS) were 42% and 44%, respectively. The addition of rituximab improved the 3-year post-transformation PFS and OS compared with combination chemotherapy alone (78% versus 15%, P < 0.00001) and (87% versus 38.5%, P < 0.00001), respectively. In multivariate analysis, only rituximab was associated with OS [HR 0.07 (95% CI 0.015-0.312, P = 0.001)] and PFS [HR 0.19 (95% CI 0.55-0.626, P = 0.007)] following transformation.Conclusions There is a moderate risk of transformation in limited-stage follicular lymphoma treated with curative intent RT, and it substantially impacts outcome in these patients. Treatment with rituximab at the time of transformation appears to improve survival in this otherwise poor-risk population.

Clinical Oncology, Mar 1, 2021

Performing a genome-wide association study (GWAS) might add to a better understanding of the deve... more Performing a genome-wide association study (GWAS) might add to a better understanding of the development of claw disorders and the need for trimming. Therefore, the aim of the current study was to perform a GWAS on claw disorders and trimming status and to validate the results for claw disorders based on an independent data set. Data consisted of 20,474 cows with phenotypes for claw disorders and 50,238 cows with phenotypes for trimming status. Recorded claw disorders used in the current study were double sole (DS), interdigital hyperplasia (IH), sole hemorrhage (SH), sole ulcer (SU), white line separation (WLS), a combination of infectious claw disorders consisting of (inter-) digital dermatitis and heel erosion, and a combination of laminitis-related claw disorders (DS, SH, SU, and WLS). Of the cows with phenotypes for claw disorders, 1,771 cows were genotyped and these cow data were used for the GWAS on claw disorders. A SNP was considered significant when the false discovery rate ≤ 0.05 and suggestive when the false discovery rate ≤ 0.20. An independent data set of 185 genotyped bulls having at least 5 daughters with phenotypes (6,824 daughters in total) for claw disorders was used to validate significant and suggestive SNP detected based on the cow data. To analyze the trait "trimming status" (i.e., the need for claw trimming), a data set with 327 genotyped bulls having at least 5 daughters with phenotypes (18,525 daughters in total) was used. Based on the cow data, in total 10 significant and 45 suggestive SNP were detected for claw disorders. The 10 significant SNP were associated with SU, and mainly located on BTA8. The suggestive SNP were associated with DS, IH, SU, and laminitis-related claw disorders. Three of the suggestive SNP were validated in the data set of 185 bulls, and were located on BTA13, BTA14, and BTA17. For infectious claw disorders, SH, and WLS, no significant or suggestive SNP associations were detected. For trimming status, 1 significant and 1 suggestive SNP were detected, both located close to each other on BTA15. Some significant and suggestive SNP were located close to SNP detected in studies on feet and leg conformation traits. Genes with major effects could not be detected and SNP associations were spread across the genome, indicating that many SNP, each explaining a small proportion of the genetic variance, influence claw disorders. Therefore, to reduce the incidence of claw disorders by breeding, genomic selection is a promising approach.

Blood, Aug 20, 2020

In light of recent publications from the Trans Tasman Radiation Oncology Group (TROG), 1 the Inte... more In light of recent publications from the Trans Tasman Radiation Oncology Group (TROG), 1 the International Lymphoma Radiation Oncology Group, 2 and the Australian Lymphoma Alliance, 3 we sought to update the long-term outcomes of computed tomographystaged limited-stage follicular lymphoma (FL) treated with radiotherapy (RT) alone. The phase 3 TROG study demonstrated that the addition of immunochemotherapy to curative-intent RT improves progression-free survival (PFS), but not overall survival (OS), at the cost of increased acute toxicities. 1 The International Lymphoma Radiation Oncology Group 2 and Australian Lymphoma Alliance studies 3 mandated positron emission tomography (PET) staging and reported excellent intermediate-term outcomes from RT alone. Thus, RT alone remains an attractive treatment option for limited-stage FL; however, given the long natural history, mature follow-up is needed to accurately define relapse risks. We previously reported the outcomes of limited-stage FL treated with curative-intent RT with a median follow-up of 7.3 years. 4 We demonstrated the safety of reducing RT fields, from conventional involved regional radiotherapy (IRRT) to involved node radiotherapy with margins # 5 cm (INRT#5cm). These smaller RT fields have since become standard of care, with the intention to reduce the risks of RT-induced toxicities without compromising disease control. Medscape Continuing Medical Education online In support of improving patient care, this activity has been planned and implemented by Medscape, LLC and the American Society of Hematology. Medscape, LLC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. Medscape, LLC designates this Journal-based CME activity for a maximum of 1.00 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 1.0 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 75% minimum passing score and complete the evaluation at http://www.medscape.org/journal/blood; and (4) view/print certificate. For CME questions, see page 1013.

Australasian Journal of Dermatology, Mar 9, 2023

The CD30‐postive lymphoproliferative disorders, including lymphomatoid papulosis and primary cuta... more The CD30‐postive lymphoproliferative disorders, including lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma, account for up to 30% of all cutaneous T‐cell lymphomas (CTCLs) and are the second most common form of CTCLs after mycosis fungoides. Both conditions differ in their clinical presentations; however, they share the expression of the CD30 antigen as a common immunophenotypic hallmark. There is a wide spectrum of management options depending on factors such as extent of disease, staging and treatment tolerability. This Clinical Practice Statement is reflective of the current clinical practice in Australia.

$Research paper thumbnail of Peritransplant Radiation Therapy in Patients With Refractory or Relapsed Hodgkin Lymphoma Undergoing Autologous Stem Cell Transplant: Long-Term Results of a Retrospective Study of the Fondazione Italiana Linfomi$

International Journal of Radiation Oncology Biology Physics, Aug 1, 2023

Blood, Nov 5, 2021

Background: Lymphoma in pregnancy is a rare and challenging diagnosis that complicates approximat... more Background: Lymphoma in pregnancy is a rare and challenging diagnosis that complicates approximately 1:6000 pregnancies. Diagnostic delay occurs frequently, as lymphoma-related symptoms may be mistakenly attributed to the pregnancy itself, and diagnostic investigations postponed or omitted. Lymphoma in pregnancy poses a series of unique therapeutic, social, and ethical challenges to the patient, her family, and the medical professionals involved. This is largely due to a paucity of published management guidelines, with current evidence based on modest case series and expert opinion. In this study we endeavoured to understand women's lived experiences during this challenging time. We performed semi-structured interviews with women previously treated for lymphoma in pregnancy, to identify both gaps in care delivery and valued interventions with the aim of informing future models of care. Methods: We retrospectively identified patients from twelve sites in Australia and New Zealand aged ≥18 years of age diagnosed with Hodgkin (HL) or non-Hodgkin lymphoma (NHL) during pregnancy or within 12 months postpartum, between 1 January 2009 and 31 December 2020. Baseline demographic characteristics, treatment details, and outcomes were collected, and semi-structured interviews were conducted via telephone with those who provided informed consent. Thematic analysis was performed using QSR Int NVivo 12 Pro (March 2020, USA) to quantify salient themes. The initial 5 transcripts were independently coded by two investigators who then reached a consensus on pre-determined codes. These codes were applied to the rest of the transcripts by one coder. The frequency of pre-determined themes was determined via descriptive statistics. Results: A total of 29 women were interviewed. Baseline demographic characteristics are documented in Table 1. The majority were diagnosed during pregnancy (14%, 28% and 17% in the 1 st, 2 nd and 3rd trimesters respectively), while 41% were diagnosed post-partum. HL was the most frequent diagnosis (48%) followed by diffuse large B cell lymphoma and primary mediastinal lymphoma (14% each). More than 90% of women received chemotherapy with 28% receiving combined modality chemoradiotherapy. Sixty-nine percent commenced chemotherapy during pregnancy (17%, 28% and 14% in the 1 st, 2 nd and 3rd trimesters respectively) and 41% commencing postpartum. In the 28% of patients who received radiotherapy, this was administered post-partum. A summary of themes identified and their frequency across the 29 transcripts are shown in Figures 1-3. Diagnostic delay attributed to pregnancy was reported by 41%. 21% of the women reported fatigue, breathlessness, weight change and musculoskeletal pain, which they felt healthcare practitioners found difficult to interpret in the context of pregnancy/postpartum period. Women recalled that their chief concerns at diagnosis were the welfare of their unborn child (41%) and a fear of dying (27%). Over half of the women (55%) reported perceived communication breakdown between health practitioners and patients. They also felt there was a lack of sensitivity in discussions around fertility preservation (45%), teratogenicity of treatment (31%), termination of pregnancy (14%) and cessation of breast-feeding (14%). Valued interventions included financial/logistic assistance from charity organisations (48%), a personal support network (45%), clinical psychology referral (31%) and emergency childcare (10%). Patients also found shared patient experiences (31%) and support groups (17%) beneficial in their treatment journey. Conclusion: To our knowledge this is the first report capturing the lived experiences of survivors of lymphoma during pregnancy. This provides us a unique opportunity to consider our management, psychosocial supports, and delivery of care to meet the needs of these women. Areas for development in future care models include increased patient advocacy, educational materials, economic, psychosocial, and childcare supports. Above all, there is scope for improved, tailored communication between health practitioners and patients, with sensitivity around embryotoxicity, pregnancy termination and adverse outcomes to foster autonomy, build trust and improve maternal wellbeing. Figure 1 Figure 1. Disclosures Greenwood: Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Gangatharan: Astrazeneca: Other: Educational Conference Funding. Hamad: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

International Journal of Radiation Oncology Biology Physics, Sep 1, 2019

IFRT or PET-guided treatment, where IFRT was restricted to patients with Deauville score (DS) ! 3... more IFRT or PET-guided treatment, where IFRT was restricted to patients with Deauville score (DS) ! 3 after 2 x ABVD.The staging images were checked centrally and our reference center has created a specification for protocol-conform IFRT, which was documented on a radiation plan for each patient prior to therapy. For the present analysis, recurrent sites documented at follow-up were correlated with the radiation plan. Infield relapse was present when the recurring sites were at least in part within the area to be irradiated; outfield relapse when there were any recurring sites outside the area to be irradiated (thus, one relapse can be both infield and outfield). Results: A total of 328 and 300 patients, respectively, were PET-negative (DS 0-2) in the CMT arm and in the PET-guided arm. Among the 328 patients who were irradiated, 3.4% experienced any acute toxicity of CTCAE grade 3 during IFRT; most frequently dysphagia (1.8%) and mucositis (0.9%).There were no grade 4 toxicities. A total of 24 second malignancies have been observed thus far, with no difference between treatment arms (5-year cumulative incidence 5.6% vs. 4.6%, pZ0.54). After median follow-up of 47 months, there were no progressions, 2 early relapses and 13 late relapses in the CMT arm, and 1 progression, 9 early relapses and 19 late relapses after chemotherapy alone. An increased rate of local recurrences was observed in the arm without IFRT: 8.7% of patients without IFRT having an infield relapse vs. 2.1% in the combined modality arm (pZ0.0003). In contrast, there was no relevant difference in the rate of outfield recurrences (3.7 % with IFRT vs. 4.7 % without IFRT, pZ0.55). Conclusion: In the population of PET-negative patients of the HD16 study it could be shown that the renunciation of consolidating radiotherapy leads to a higher rate of local and early recurrences, indicating that the PFS differences observed in HD16 are in fact attributed to IFRT. The therapyassociated side effects of IFRT were marginal and the incidence of second malignancies was not increased thus far. IFRT should continue to be considered standard after 2 cycles of ABVD to avoid intensive and toxic salvage therapies such as autologous stem cell transplantation.

International Journal of Radiation Oncology Biology Physics, Jun 1, 2023

$Research paper thumbnail of Are dynamic or fixed FDG‐PET measures of disease of greater prognostic value in patients with relapsed/refractory diffuse large B‐cell lymphoma undergoing autologous haematopoietic stem cell transplantation?$

British Journal of Haematology, Apr 4, 2023

British Journal of Haematology, Mar 7, 2023

SummaryLymphoma in pregnancy (LIP) presents unique clinical, social and ethical challenges; howev... more SummaryLymphoma in pregnancy (LIP) presents unique clinical, social and ethical challenges; however, the evidence regarding this clinical scenario is limited. We conducted a multicentre retrospective observational study reporting on the features, management, and outcomes of LIP in patients diagnosed between January 2009 and December 2020 at 16 sites in Australia and New Zealand for the first time. We included diagnoses occurring either during pregnancy or within the first 12 months following delivery. A total of 73 patients were included, 41 diagnosed antenatally (AN cohort) and 32 postnatally (PN cohort). The most common diagnoses were Hodgkin lymphoma (HL; 40 patients), diffuse large B‐cell lymphoma (DLBCL; 11) and primary mediastinal B‐cell lymphoma (PMBCL; six). At a median follow up of 2.37 years, the 2‐ and 5‐year overall survival (OS) for patients with HL were 91% and 82%. For the combined DLBCL and PMBCL group, the 2‐year OS was 92%. Standard curative chemotherapy regimens were successfully delivered to 64% of women in the AN cohort; however, counselling regarding future fertility and termination of pregnancy were suboptimal, and a standardised approach to staging lacking. Neonatal outcomes were generally favourable. We present a large multicentre cohort of LIP reflecting contemporary practice and identify areas in need of ongoing research.

Journal of The American Academy of Dermatology, 2021

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

British Journal of Haematology