Radiotherapy dose response in bulky relapsed/refractory large B-cell lymphoma.

PURPOSE: To assess whether a radiotherapy (RT) dose affects response in bulky tumors in relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL). METHODS: Data from r/r DLBCL patients treated with salvage- or palliative-intent RT (2008-2020) at a single institution were examined. Index lesion size ≥7.5 cm was defined as bulky. Equivalent doses in 2 Gray (Gy) fractions (EQD2) were calculated to compare doses between conventional and hypofractionated (HF, ≥2.5 Gy/fraction) schemes. Objective response rates (ORR) were compared using non-parametric Mann-Whitney U test or Kruskal-Wallis tests with Dunn's multiple comparison corrections. Freedom from local progression (FFLP) was assessed using Kaplan-Meier and Cox proportional hazard regression analyzes. RESULTS: 183 courses of 151 unique patients were included (salvage: 37%, palliative: 63%). Non-bulky and bulky tumors were irradiated in 109 (60%) and 74 (40%) courses, respectively. Median EQD2 was 33 Gy (IQR=23-39 Gy) with HF in 84 (46%) cases. Of those with post-RT imaging (80%), the ORR was 59% with a trend towards worsened ORR in bulky tumors (50% vs. 65%, p=0.077). For bulky tumors, RT regimens with EQD2s >30 Gy were associated with better ORR (≤30 Gy vs. >30 Gy: 27% vs. 64%, p=0.0073), whereas a lower EQD2 cut-off was sufficient for non-bulky tumors (≤20 Gy vs. >20 Gy: 38% vs. 75%, p=0.0011). On multivariable regression, bulky tumor size was associated with worsened FFLP (HR=2.07, 95% CI=1.16-3.68, p=0.014), while high EQD2s >30 Gy were associated with better FFLP (HR=0.48, 95% CI=0.25-0.93, p=0.031). Bulky tumors treated with EQD2s ≤30 Gy had the lowest median FFLP (4.0 months), while EQD2s >30 Gy had an unreached median FFLP (p=0.0047). CONCLUSIONS: Bulky r/r DLBCL tumors were associated with less favorable tumor control outcomes in the salvage and palliative settings. RT regimens with higher EQD2s (>30 Gy) should be considered if durable local control of bulky tumors is desired.

International Prognostic Score for Nodular Lymphocyte-Predominant Hodgkin Lymphoma.

PURPOSE: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer, and large international cooperative efforts are needed to evaluate the significance of clinical risk factors and immunoarchitectural patterns (IAPs) for all stages of pediatric and adult patients with NLPHL. METHODS: Thirty-eight institutions participated in the Global nLPHL One Working Group retrospective study of NLPHL cases from 1992 to 2021. We measured progression-free survival (PFS), overall survival (OS), transformation rate, and lymphoma-specific death rate. We performed uni- and multivariable (MVA) Cox regression stratified by management to select factors for the lymphocyte-predominant international prognostic score (LP-IPS) validated by five-fold cross-validation. RESULTS: We identified 2,243 patients with a median age of 37 years (IQR, 23-51). The median follow-up was 6.3 years (IQR, 3.4-10.8). Most had stage I to II (72.9%) and few B symptoms (9.9%) or splenic involvement (5.4%). IAP was scored for 916 (40.8%). Frontline management included chemotherapy alone (32.4%), combined modality therapy (30.5%), radiotherapy alone (24.0%), observation after excision (4.6%), rituximab alone (4.0%), active surveillance (3.4%), and rituximab and radiotherapy (1.1%). The PFS, OS, transformation, and lymphoma-specific death rates at 10 years were 70.8%, 91.6%, 4.8%, and 3.3%, respectively. On MVA, IAPs were not associated with PFS or OS, but IAP E had higher risk of transformation (hazard ratio [HR], 1.81; P < .05). We developed the LP-IPS with 1 point each for age ≥45 years, stage III-IV, hemoglobin <10.5 g/dL, and splenic involvement. Increasing LP-IPS was significantly associated with worse PFS (HR, 1.52) and OS (HR, 2.31) and increased risk of lymphoma-specific death (HR, 2.63) and transformation (HR, 1.41). CONCLUSION: In this comprehensive study of all ages of patients with NLPHL, we develop the LP-IPS to identify high-risk patients and inform upcoming prospective clinical trials evaluating de-escalation of therapy for patients with low LP-IPS scores (<2).

The elephant's other legs: What some sciences actually do.

Integrative experiments, as described, seem blindly empirical, as if the question of generality of effects could not be understood through controlled one-at-a-time experiments. But current research using such experiments, especially applied research, can resolve issues and make progress through understanding of cause-effect pathways, leaving to engineers the task of translating this understanding into practice.

Individual differences and multi-step thinking.

Deliberative thinking often consists of several steps, each involving a switch decision. These decisions may be influenced by confidence in the thinking done so far. Individuals may differ in their tolerance of low confidence and thus may arrive at unjustified high confidence too soon, either from trusting their intuition or by bolstering an initially favored conclusion.

Salvage radiotherapy for relapsed/refractory non-Hodgkin lymphoma following CD19 chimeric antigen receptor T-cell (CART) therapy.

Background and purpose: CD19-targeting chimeric antigen receptor T-cell (CART) therapy is a promising treatment for relapsed/refractory non-Hodgkin lymphoma, but most patients experience post-CART progression. We describe our institutional experience of salvage radiotherapy (SRT) in this setting. Materials and methods: Of 94 patients who received CART therapy from 2018 to 2020, 21 received SRT for post-CART progression. Patients were divided into two groups: locoregional disease (n = 9 [43 %], all disease encompassable within an RT field) and advanced disease (n = 12 [57 %]). Patterns of failure, progression-free survival (PFS), overall survival (OS), and toxicity were assessed. Results: Median time from CART infusion to SRT was 4.0 months (range, 0.6-11.5 months). In the locoregional disease group, 8/9 patients (89 %) were treated with comprehensive SRT to a median dose of 37.5 Gy in a median of 15 fractions. In the advanced disease group, all patients (n = 12) were treated with focal SRT to a median dose of 20.8 Gy in a median of 5 fractions. Median follow-up post-SRT was 15.2 months. In-field response was observed in 8/9 (89 %) in the locoregional disease and 8/9 (89 %) evaluable patients in the advanced disease groups. 17/18 evaluable patients (94 %) patients experienced post-SRT progression, all with a distant component. Median OS was 7.4 months; 21 months for locoregional disease versus 2.4 months for advanced disease (p = 0.0002). Median PFS was 1.1 month, and similarly poor regardless of group. No grade ≥ 3 toxicities occurred. Conclusions: SRT post-CART therapy appears safe with encouraging in-field response but high rates of out-of-field progression, even for those presenting with locoregional disease, highlighting the need for integration of novel systemic agents.

Proton Radiation Therapy After Chemotherapy in the Management of Aggressive Mediastinal Non-Hodgkin Lymphomas: A Particle Therapy Cooperative Group Lymphoma Subcommittee Collaboration.

Purpose: Combined modality therapy with multiagent chemotherapy and radiation therapy is a standard treatment option for aggressive mediastinal non-Hodgkin lymphomas (AMNHLs); however, concerns regarding acute and late radiation toxicities have fueled an effort to use systemic therapy alone. The use of proton therapy (PT) is a promising treatment option, but there are still limited data regarding clinical outcomes with this treatment modality. In this Particle Therapy Cooperative Group lymphoma subcommittee collaboration, we report outcomes of patients with AMNHL treated with pencil-beam scanning PT or double-scatter PT after chemotherapy. Methods and Materials: This was a multi-institutional retrospective observational cohort study of patients with AMNHL treated with PT following chemotherapy between 2011 and 2021. Progression-free survival (PFS), local recurrence-free survival (LRFS), and overall survival (OS) rates were estimated with the Kaplan-Meier method. PT toxicity was graded by the Common Terminology Criteria for Adverse Events version 5.0. A 2-tailed paired t test was used for dosimetric comparisons. Results: Twenty-nine patients were identified. With a median follow-up time of 4.2 years (range, 0.2-8.9 years), the estimated 5-year PFS for all patients was 93%, 5-year LRFS was 96%, and estimated 5-year OS was 87%. Maximum acute grade 1 (G1) toxicities occurred in 18 patients, and 7 patients had maximum G2 toxicities. No G3+ radiation-related toxicities were observed. Average mean lung dose and lung V20 Gy were lower for patients treated with pencil-beam scanning PT compared with double-scatter PT (P = .016 and .006, respectively), while patients with lower mediastinal disease had higher doses for all evaluated dosimetric heart parameters. Conclusions: PT after chemotherapy for patients with AMNHL resulted in excellent outcomes with respect to 5-year PFS, LRFS, and OS without high-grade toxicities. Future work with larger sample sizes is warranted to further elucidate the role of PT in the treatment of AMNHL.

Radiation Therapy for Relapsed or Refractory Diffuse Large B-Cell Lymphoma: What Is the Right Regimen for Palliation?

Purpose: To report objective response rates (ORR), time to local failure (TTLF), and overall survival (OS) among patients with relapsed or refractory diffuse large B-cell lymphoma after salvage- or palliative-intent radiation therapy (RT) and to investigate whether outcomes differed with conventional versus hypofractionated (≥2.5 Gy/fraction) RT. Methods and Materials: A single-institution observational cohort study was performed for patients who completed a course of RT for relapsed or refractory diffuse large B-cell lymphoma between January 1, 2008, and April 1, 2020. Predictors of ORR, TTLF, and OS were calculated using univariable and multivariable regression models. The Kaplan-Meier method was used to estimate TTLF and OS, and log-rank analysis was used to compare outcomes. Equivalent dose in 2 Gy fractions (EQD2) was calculated using an α/ß of 10. Results: One-hundred and sixty-nine patients were treated with 205 RT courses (73 [36%] salvage, 132 [64%] palliative), and hypofractionated RT was used in 100 RT courses (49%). Median RT dose was 30 Gy (range, 8-60 Gy). ORR was 60% for the total cohort (53% and 69% for palliative and salvage cohorts, respectively). Over a median follow-up time of 4 months, median OS in all patients was 5 months (3 and 22 months for palliative and salvage cohorts, respectively). No statistically significant differences in ORR, TTLF, and OS were observed with hypofractionation compared with conventional fractionation. EQD2 ≥35 Gy was associated with improved ORR (odds ratio, 3.79 [1.19-12.03]; P = .024) and prolonged TTLF (0.39 [0.18-0.87]; P = .022), while double-hit receptor status (8.18 [1.08-62.05]; P = .042), cell of origin (3.87 [1.17-8.74]; P = .0012), and bulky disease (≥7.5 cm; 2.12 [1.18-3.81]; P = .012) were associated with inferior TTLF. In the palliative-only cohort, a low-dose regimen of 8 Gy in 2 fractions was associated with similar ORR compared with other fractionation schema but trended towards inferior TTLF (P = .36). Conclusions: Hypofractionation is not associated with differences in disease outcomes for patients with relapsed or refractory diffuse large B-cell lymphoma, while higher RT dose (EQD2 ≥35 Gy) may improve ORR and TTLF. Future work is warranted to elucidate the ideal dose and fractionation schema for such patients who will likely also undergo novel systemic agents and cellular therapies.

Dosimetric Results for Adjuvant Proton Radiation Therapy of HPV-Associated Oropharynx Cancer.

Purpose: One significant advantage of proton therapy is its ability to improve normal tissue sparing and toxicity mitigation, which is relevant in the treatment of oropharyngeal squamous cell carcinoma (OPSCC). Here, we report our institutional experience and dosimetric results with adjuvant proton radiation therapy (PRT) versus intensity-modulated radiotherapy (IMRT) for Human Papilloma Virus (HPV)-associated OPSCC. Materials and Methods: This was a retrospective, single institutional study of all patients treated with adjuvant PRT for HPV-associated OPSCC from 2015 to 2019. Each patient had a treatment-approved equivalent IMRT plan to serve as a reference. Endpoints included dosimetric outcomes to the organs at risk (OARs), local regional control (LRC), progression-free survival (PFS), and overall survival (OS). Descriptive statistics, a 2-tailed paired t test for dosimetric comparisons, and the Kaplan-Meier method for disease outcomes were used. Results: Fifty-three patients were identified. Doses delivered to OARs compared favorably for PRT versus IMRT, particularly for the pharyngeal constrictors, esophagus, larynx, oral cavity, and submandibular and parotid glands. The achieved normal tissue sparing did not negatively impact disease outcomes, with 2-year LRC, PFS, and OS of 97.0%, 90.3%, and 97.5%, respectively. Conclusion: Our study suggests that meaningful normal tissue sparing in the postoperative setting is achievable with PRT, without impacting disease outcomes.

Low-Dose Radiotherapy Versus Moderate-Dose Radiotherapy for the Treatment of Indolent Orbital Adnexal Lymphomas.

PURPOSE: Radiation therapy (RT) with doses ranging from 24 Gray (Gy) to 40 Gy is a proven treatment modality for indolent orbital adnexal lymphoma (IOAL), but recently the use of low dose RT (LDRT, defined as 2 Gy x 2 fractions) has become a notable alternative. However, limited data exists comparing outcomes following LDRT to moderate-dose RT (MDRT, RT dose 4 - 36 Gy). We present a single institution retrospective analysis comparing outcomes of patients with IOALs following LDRT or MDRT. METHODS: A total of 36 patients treated with 38 consecutive courses of RT were identified; LDRT was delivered for 14 courses and MDRT for 24 courses. Overall response rates (ORR) were recorded according to Deauville or RECIST criteria with a response characterized as a complete response (CR) or partial response. Local control (LC), orbital control (OC), and overall survival (OS) rates were estimated with the Kaplan-Meier method. RT toxicity was graded per CTCAEv5 and compared with the Fisher's exact test. RESULTS: Median follow-up time was 29 months (m) (range, 4-129m), and median MDRT dose used was 24 Gy (range 21-36 Gy). Overall response rates (ORR) were 100% (CR 50%) and 87.5% (CR 58.3%) following LDRT and MDRT, respectively. OS at 2 years was 100% and 95% for the LDRT and MDRT groups, respectively (p=0.36). LC rates at 2 years was 100% for both LDRT and MDRT groups and at 4 years was 100% and 89% for the LDRT and MDRT groups, respectively (p=0.56). The 4-year OC rate (including both ipsilateral and contralateral relapses) was 80% and 85% for the LDRT and MDRT groups, respectively (p=0.79). No patient required treatment with RT to a previously irradiated orbit. Acute toxicities were reported following 6 LDRT courses compared to 20 MDRT courses (p=.014). No Grade 3 or higher acute toxicities occurred in either group. Late toxicities were reported following 2 LDRT courses compared to 10 MDRT courses (p=0.147). CONCLUSIONS: LDRT produced similar ORR, LC, OC, and OS rates compared to MDRT with fewer acute and minimal late toxicities reported. Future multi-center studies with larger patient numbers are warranted to show significant associations.

Palliative Radiotherapy for Diffuse Large B-cell Lymphoma.

Recent improvements in chemoimmunotherapies, targeted agents, hematopoietic stem cell transplants, and cellular therapies have revolutionized treatment paradigms for patients with diffuse large B-cell lymphoma (DLBCL). Even in the relapsed or refractory setting, contemporary treatment options are delivered with curative intent and can lead to lasting remissions. Although such therapies have improved overall outcomes, they have increasingly led to a wide variety of presentations of recurrent tumors in need of palliation. Here, we review the use of radiotherapy (RT) in the palliation of DLBCL. We draw particular attention to the evolving role for hypofractionated RT and low-dose RT for DLBCL. We review the available literature on these topics and focus on commonly encountered clinical scenarios.

Radiation Therapy for Chemotherapy Refractory Gingival Myeloid Sarcoma.

Gingival myeloid sarcoma (MS) refractory to induction chemotherapy is a rare clinical entity and can be treated with palliative radiation therapy (RT). However, there are few previously published reports of RT approaches for the treatment of gingival MS. We present a single institution retrospective observational study of adult patients treated with palliative RT for chemotherapy refractory gingival MS. A total of six patients diagnosed with gingival MS in the setting of relapsed or refractory acute myeloid leukemia treated with palliative RT were identified, with a median age of 66 (range 52-77). Patients were treated with radiation doses ranging from 5 to 20 Gy in 2-10 fractions. Two patients had adequate follow-up time to assess treatment response. One patient who was simulated with PET/CT experienced a local complete response, while the other patient required retreatment 2 months after initial treatment and experienced an eventual local partial response. Three patients experienced radiation mucositis, with one patient experiencing grade 5 toxicity attributed to concomitant treatment with the radiosensitizer hydroxyurea. We believe that this study can provide a practical reference point for other clinicians given the rarity of gingival MS requiring palliative radiation therapy as a clinical entity.

Bridging Radiation Therapy Before Commercial Chimeric Antigen Receptor T-Cell Therapy for Relapsed or Refractory Aggressive B-Cell Lymphoma.

PURPOSE: CD19-targeting chimeric antigen receptor T-cell (CART) therapy has emerged as a promising treatment for relapsed/refractory aggressive B-cell lymphoma (r/rABL), culminating in 2 US Food and Drug Administration-approved therapies: tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel). Following leukapheresis and in preparation for CART infusion, contemporary bridging and lymphodepletion regimens rely mostly on cytotoxic chemotherapy. Here, in a cohort of patients treated with commercial tisa-cel and axi-cel, we show that bridging-RT may offer a supplemental approach. METHODS AND MATERIALS: Thirty-one patients receiving commercial tisa-cel (n = 13) or axi-cel (n = 18) between August 2018 and February 2019 for r/rABL were retrospectively reviewed. Patients were categorized into 2 groups: (1) bridging-RT within 30 days of CART infusion or (2) nonbridging-RT (NBRT), in which patients received either remote RT greater than 30 days before CART infusion or no prior RT. RESULTS: Five patients received bridging-RT within 30 days of CART infusion. Median bridging-RT dose was 37.5 Gy and was completed a median of 13 days before infusion. No grade 3 (G3) or higher RT-toxicities occurred. No patients in the bridging-RT group experienced G3 or higher CART-related toxicities (CRS or neurotoxicity), and 23% (n = 6) and 15% (n = 4) experienced G3-5 CRS and G3-5 neurotoxicity in the NBRT group, respectively. Overall treatment response in the bridging-RT and NBRT groups was 80% and 64%, respectively. The axi-cel CART product was associated with CRS (odds ratio [OR] = 26.67, P = .001) and CRS correlated with neurotoxicity (OR = 12.22, P = .028). There was a trend toward an association for CRS with metabolic tumor volume (OR = 1.06/mL, P = .141) and TLG (OR = 1.01/mL x standard uptake value, P = .099). CONCLUSIONS: Bridging-RT before commercial CART does not appear to increase the risk for CART-related toxicities or negatively affect outcomes in r/rABL patients. No G3 or higher RT-toxicities occurred in this series. Pretreatment metabolic tumor burden may be associated with CART-associated CRS; however, larger patient numbers are required to elucidate significant associations. Future work to prospectively assess the value of bridging-RT is warranted.

False Equivalence: Are Liberals and Conservatives in the United States Equally Biased?

On the basis of a meta-analysis of 51 studies, Ditto et al. (this issue, p. 273) conclude that ideological bias is equivalent on the left and right of U.S. politics. In this commentary, we contend that this conclusion does not follow from the review and that Ditto and his colleagues are too quick to embrace a false equivalence between the liberal left and the conservative right. For one thing, the issues, procedures, and materials used in the studies reviewed by Ditto and his colleagues were selected for purposes other than the inspection of ideological asymmetries. Consequently, methodological choices made by researchers were systematically biased to avoid producing differences between liberals and conservatives. We also consider the broader implications of a normative analysis of judgment and decision making and demonstrate that the bias examined by Ditto and his colleagues is not, in fact, an irrational bias, and that it is incoherent to discuss bias in the absence of standards for assessing accuracy and consistency. Other conclusions about domain-general asymmetries in motivated social cognition have suggested that epistemic virtues are more prevalent among liberals than conservatives, and these conclusions are closer to the truth of the matter when it comes to current American politics. Finally, we question the notion that the research literature in psychology is necessarily characterized by liberal bias, as several authors have claimed.

Mobile platform for rapid sub-picogram-per-milliliter, multiplexed, digital droplet detection of proteins.

Digital droplet assays-in which biological samples are compartmentalized into millions of femtoliter-volume droplets and interrogated individually-have generated enormous enthusiasm for their ability to detect biomarkers with single-molecule sensitivity. These assays have untapped potential for point-of-care diagnostics but are currently mainly confined to laboratory settings, due to the instrumentation necessary to serially generate, control, and measure tens of millions of droplets/compartments. To address this challenge, we developed an optofluidic platform that miniaturizes digital assays into a mobile format by parallelizing their operation. This technology is based on three key innovations: (i) the integration and parallel operation of a hundred droplet generators onto a single chip that operates >100× faster than a single droplet generator, (ii) the fluorescence detection of droplets at >100× faster than conventional in-flow detection using time domain-encoded mobile phone imaging, and (iii) the integration of on-chip delay lines and sample processing to allow serum-to-answer device operation. To demonstrate the power of this approach, we performed a duplex digital ELISA. We characterized the performance of this assay by first using spiked recombinant proteins in a complex media (FBS) and measured a limit of detection, 0.004 pg/mL (300 aM), a 1,000× improvement over standard ELISA and matching that of the existing laboratory-based gold standard digital ELISA system. We additionally measured endogenous GM-CSF and IL6 in human serum from n = 14 human subjects using our mobile duplex assay, and showed excellent agreement with the gold standard system ([Formula: see text]).

Actively open-minded thinking in politics.

The concept of actively open-minded thinking (AOT) provides standards for evaluation of thinking, which apply both to our own thinking and to the thinking of others. AOT is important for good citizenship for three reasons: it provides a prescription for individual thinking about political decisions; it serves as a social norm (when others agree); and, perhaps most importantly, it provides a standard for knowing which sources to trust, including politicians and pundits. I provide a current account of AOT as a general prescriptive theory that defines a standard or norm for all thinking, with emphasis on its role in the judgment of the thinking of others, and in maintaining appropriate confidence. I also contrast AOT with other standards. AOT does not assume that more thinking is always better, and it implies that low confidence in the results of thinking is often warranted and beneficial. I discuss the measurement of AOT and its relation to politics. Finally, I report two preliminary studies of AOT in judgments of others thoughts, and the role of confidence.

Forms of explanation and why they may matter.

Explanations from neuroscience are threatening to replace those from psychology in the eyes and hands of journalists, university administrators, granting agencies, and research students. If replacement happens, much of psychology will exist only as part of the historical record. It, thus, may be useful to understand what forms of explanation are used by the two fields. Such an understanding may help us explain how each field can contribute to the other and why they are different. I review several templates of psychological and neuroscientific explanation, and criticize some others. I argue that psychology (and neuroscience) should continue to exist. Neuroscience is not better than psychology, and it cannot replace psychology.

Correlations of trait and state emotions with utilitarian moral judgements.

In four experiments, we asked subjects for judgements about scenarios that pit utilitarian outcomes against deontological moral rules, for example, saving more lives vs. a rule against active killing. We measured trait emotions of anger, disgust, sympathy and empathy (the last two in both specific and general forms, the latter referring to large groups of people), asked about the same emotions after each scenario (state emotions). We found that utilitarian responding to the scenarios, and higher scores on a utilitarianism scale, were correlated negatively with disgust, positively (but weakly and inconsistently) with anger, positively with specific sympathy and state sympathy, and less so with general sympathy or empathy. In a fifth experiment, we asked about anger and sympathy for specific outcomes, and we found that these are consistently predictive of utilitarian responding.

Individual Mental Abiities vs. the World's Problems.

The major problems in the world today are problems of government or the lack of it. Thus, the relevant parts of intelligence are those that make for good citizenship, such as supporting the best candidates and policies. I argue that dispositions, as well as capacities, are part of intelligence, and that some dispositions are the ones most crucial for citizenship, particularly the disposition to engage in actively open-minded thinking (AOT) and to apply it as a standard for the evaluation of the qualifications of authorities and leaders. AOT is a general prescriptive theory that applies to all thinking. It affects the aptness of conclusions and the accuracy of confidence judgments, and it reduces overconfidence when extreme confidence is not warranted. AOT may be affected by different factors from those that affect other components of intelligence and thus may undergo different changes over time. Whatever has happened in the past, we need more of it now.

Anti-profit beliefs: How people neglect the societal benefits of profit.

Profit-seeking firms are stereotypically depicted as immoral and harmful to society. At the same time, profit-driven enterprise has contributed immensely to human prosperity. Though scholars agree that profit can incentivize societally beneficial behaviors, people may neglect this possibility. In 7 studies, we show that people see business profit as necessarily in conflict with social good, a view we call anti-profit beliefs. Studies 1 and 2 demonstrate that U.S. participants hold anti-profit views of real U.S. firms and industries. Study 3 shows that hypothetical organizations are seen as doing more harm when they are labeled "for-profit" rather than "non-profit," while Study 4 shows that increasing harm to society is viewed as a strategy for increasing a hypothetical firm's long-run profitability. Studies 5-7 demonstrate that carefully prompting subjects to consider the long run incentives of profit can attenuate anti-profit beliefs, while prompting short run thinking does nothing relative to a control. Together, these results suggest that the default view of profits is zero-sum. While people readily grasp how profit can incentivize firms to engage in practices that harm others, they neglect how it can incentivize firms to engage in practices that benefit others. Accordingly, people's stereotypes of profit-seeking firms are excessively negative. Even in one of the most market-oriented societies in history, people doubt the contributions of profit-seeking industry to societal progress. (PsycINFO Database Record