Neoadjuvant Osimertinib Followed by Sequential Definitive Radiation Therapy and/or Surgery in Stage III Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer: An Open-Label, Single-Arm, Phase 2 Study.

PURPOSE: The treatment for unresectable, locally advanced stage III non-small cell lung cancer (NSCLC) is concurrent chemoradiation therapy (CRT) followed by consolidation durvalumab. This study aimed to evaluate the benefit of neoadjuvant osimertinib as an alternative therapy to this approach with the aim of reducing the radiation field. METHODS AND MATERIALS: This investigation was a nonrandomized, open-label, single-arm, phase 2, prospective, proof-of-concept study. Eligible patients were classified as having treatment-naïve, nonoperable, stage III epidermal growth factor receptor-mutant NSCLC. Patients received 80 mg of oral osimertinib daily for 12 weeks before definitive radiation therapy (RT) and/or surgery. The response was assessed at weeks 6 and 12. For responders, sequential definitive RT and/or surgery were planned. Nonresponders were started on standard CRT. After RT ± surgery or CRT, patients were followed for 2 years without adjuvant therapy. The primary endpoint was the objective response rate (ORR), with September 20, 2022, set as the cut-off for data collection. Secondary endpoints were safety and the gross tumor volume (GTV), planned tumor volume (PTV), and the percentage of total lung volume minus GTV exceeding 20 Gy (V20%) before versus after osimertinib. Exploratory analyses included assessments of the presence of plasma circulating tumor-free DNA (ctDNA) before osimertinib treatment, at weeks 6 and 12, at the end of RT, and 6 weeks post-RT. RESULTS: Twenty-four patients were included (19 women; median age, 73 years; range, 51-82 years). Nineteen of 24 had never smoked, 20 of 24 had adenocarcinoma, 16 of 24 had exon 19 deletions, and 8 of 24 had exon 21 mutations. Participants had stage IIIA (10), IIIB (9), or IIIC (5) disease. Three patients were excluded from the analysis (1 dropped out and 2 were still undergoing osimertinib treatment at the cut-off date). The ORR to induction osimertinib was 95.2% (17 partial response, 3 complete response, and 1 progressive disease). After induction osimertinib, 13 of 20 patients were definitively radiated, 3 of 20 underwent surgery, and 5 of 20 were excluded. Four patients were restaged as stage IV (contralateral ground-glass opacities responded to osimertinib), and 1 patient withdrew informed consent. Three patients underwent surgery, one of whom was treated with RT. Two patients achieved pT1aN0, and one achieved pathologic complete response. The median GTV, PTV, and V20% before osimertinib treatment were 47.4 ± 76.9 cm3 (13.5-234.9), 227.0 ± 258.8 cm3 (77.8-929.2), and 27.1 ± 16.4% (6.2-60.3), respectively. The values after osimertinib treatment were 27.5 ± 42.3 cm3 (2.99-137.7; -48 ± 20%; P = .02), 181.9 ±198.4 cm3 (54-718.1; -31 ± 20%; P = .01), and 21.8 ± 11.7% (9.1-44.15; -24 ± 40%; P = .04), respectively. PTV/GTV/V20% reduction was associated with tumor size and central location. The median follow-up time was 28.71 months (range, 0.4-45.1 months), and median disease-free survival was not reached (mean, 30.59; standard error, 3.94; 95% confidence interval, 22.86-38.31). ctDNA was detected in 5 patients; 4 of 5 were positive for ctDNA at baseline and became negative during osimertinib induction but were again positive after osimertinib treatment was terminated. Interestingly, 3 patients who were ctDNA negative at baseline became weakly positive after RT and then were negative at follow-up. No significant adverse events were reported during the osimertinib or radiation phases. CONCLUSIONS: Neoadjuvant osimertinib therapy is feasible in patients with stage III lung cancer NSCLC, followed by definitive radiation and/or surgery, with an ORR of 95.2% and an excellent safety profile. Osimertinib induction for 12 weeks before definitive radiation (chemo-free) significantly reduced the radiation field by nearly 50% with a linear association with tumor size. Further studies are needed to test this chemo-free approach for long-term outcomes before practices are changed.

Is prostate cancer screening justified in the Bedouin population?

BACKGROUND: The aim of the study was to investigate whether the awareness of prostate cancer among Bedouin men is low or whether the incidence of prostate cancer is truly low among the Bedouin population. PATIENTS AND METHODS: Total prostate-specific antigen (PSA) levels were measured in 206 men aged > or =50 out of 1,221 male inhabitants of a geographically defined population from the Negev desert surrounding Beer Sheva. RESULTS: The average PSA level was 1.67 ng/ml (range 0.07-22.1). Abnormal PSA levels were present in 13 out of 206 subjects. Only 10 of these agreed to have trans-rectal ultrasound (TRUS) and biopsy, 3 subjects refused further investigation by digital rectal examination (DRE) and TRUS. The average number of biopsies was 8 (range 6-10). Prostate cancer was not confirmed. The histological diagnosis was benign prostatic hyperplasia (BPH) or chronic inflammation. CONCLUSION: The Bedouin men from a geographically defined population from the Negev desert surrounding Beer Sheva have low PSA serum concentration. The incidence rate of prostate cancer is very low and screening is unjustified in the asymptomatic Bedouin population.

Semi-automatic volumetric measurement of response to chemotherapy in lung cancer patients: How wrong are we using RECIST?

OBJECTIVES: Lung cancer typically starts as a near-spherical lesion, but as it grows it may acquire an irregular radiologic formation. RECIST is based on the assumption that tumors are spherical, and consequently, proportional changes of tumor volume and parallel changes in tumor diameter, and vice versa. Hence, a 30% decrease in diameter (2r) implies a 65% decrease of volume, and a 20% increase in diameter implies a 73% increase of volume. MATERIALS AND METHODS: We compared volumetric measurement based on multi-detector CT technology with calculated volume (CV) according to RECIST in a cohort of 43 patients with advanced, non-squamous cell type, lung cancer treated with a combination of platinum and pemetrexed. RESULTS: CV was larger than SMV in most patients both at baseline and at best overall response (BOR). The difference between the sum of volumes based on volumetric measurement (SMV) and CV was larger for higher sum of diameters. The Lin's concordance correlation coefficient between the percent changes in SMV and CV at BOR was 0.757. Of note, four patients (4/43, 9.5%) were categorized as PD according to the method of CV, but SD according to the method of SMV. CONCLUSION: Our study highlights the importance of volumetric measurement for assessing response to treatment in lung cancer patients particularly showing large, irregular lesions.

Colorectal cancer in southern Israel: Comparison between Bedouin Arab and Jewish patients.

PURPOSE: Colorectal cancer (CRC) is the second most common malignancy and the third leading cause of cancer deaths in Israel; it is less common among the Arab than the Jewish population. This study compares the clinico-pathologic features, treatment, and prognosis between Bedouin-Arab (BA) and Jewish CRC patients treated at our medical centre. METHODS: The medical records of 56 BA patients with CRC were compared retrospectively to 115 Jewish patients. Collected data included age, gender, history of smoking, family history of cancer, presenting symptoms, laboratory tests, previous malignancy, tumor characteristics, surgery type, stoma formation and closure, types of adjuvant treatment, and outcome. RESULTS: BA patients were younger (mean age 68 versus 57 years, p < 0.001), showed a higher incidence in females (p = 0.045), and had a lower frequency of a family history of cancer (p = 0.005) compared to Jewish patients. BA patients had a higher presentation of rectal bleeding and a lower rate of anemia at tumor diagnosis (p = 0.05 and p = 0.004, respectively) with a more distal location of the tumor (p = 0.003). BA patients more often received chemotherapy and radiotherapy (p = 0.02 and p = 0.04, respectively). Disease-free survival was shorter among BA patients (p = 0.023); overall survival was similar in both groups. CONCLUSIONS: CRC in BAs is characterized by a higher proportion of female, younger age, and higher proportion of distal location compared to Jewish patients. These differences in biology may be related to differences in past lifestyles and diet of BA compared to Jewish patients, and are expected to decrease in the following years as the BA population continues to undergo "westernization" changes.

CD20 Over-Expression in Hodgkin-Reed-Sternberg Cells of Classical Hodgkin Lymphoma: the Neglected Quest.

We have scrutinized a previously analyzed cohort of classical Hodgkin lymphoma patients for evidence of a CD20 over-expression. This was pursued in order to determine whether all the 24 (12.6%) CD20+++ patients had clinical and/or biological profiles which would warrant a separate consideration and treatment or would carry a different outcome from our 166 CD20 (-) classical Hodgkin lymphoma patients. Except for an older age and a significantly lower expression of non-sialyl-CD15 antigen, both previously described in classical Hodgkin lymphoma, no justification to exclude these CD20+++ patients from the cohort at large is apparent. We suggest that the generally accepted view to the contrary be revised. In addition, we propose alternative interpretations for the low expression of CD20 found in a majority of Hodgkin-Reed-Sternberg cells in classical Hodgkin lymphoma.

Two Paraneoplastic Autoimmune Syndromes: Limbic Encephalitis and Palmar Fasciitis in a Patient with Small Cell Lung Cancer.

Small cell lung cancer (SCLC) is characterized by a relatively high rate of autoimmune phenomena. Paraneoplastic limbic encephalitis (PLE) is an autoimmune syndrome in which a non-neural tumor containing an antigen normally present in the nervous system precipitates an antibody attack on neural tissues. Patients with PLE usually present with rapidly progressive short-term memory deficits, confusion or even dementia. Palmar fasciitis and polyarthritis syndrome (PFPAS) is another autoimmune syndrome characterized by rheumatologic manifestations, especially involving the palms of the hands. We report a case of a 59-year old woman who presented with worsening neurological symptoms of two-week duration, and later coma. The combined clinical, serological, and imaging studies suggested a diagnosis of PLE. A chest computed tomographic scan showed a 1.2 cm-diameter mass in the upper lobe of the left lung that was surgically removed and showed SCLC. Following surgery, neurological symptoms rapidly improved, allowing the patient to receive adjuvant chemotherapy. While in remission for both SCLC and PLE, the patient developed pain, soft-tissue swelling, and stiffness in both palms, suggesting the diagnosis of PFPAS. Five months following the diagnosis of palmar fasciitis, SCLC relapsed with mediastinal and cervical lymphadenopathy. This case report underlines the continuous interaction of SCLC with the immune system, expressed by coexistence of two rare paraneoplastic diseases, PLE, and PFPAS, in a patient with SCLC. While symptoms related to PLE preceded the initial diagnosis of SCLC, other symptoms related to PFPAS preceded relapse.

Breast cancer in Bedouin-Arab patients in southern Israel: epidemiologic and biologic features in comparison with Jewish patients.

BACKGROUND: Breast cancer (BC) is the most frequent cancer type, and the leading cause of death from cancer among women in Israel. The Bedouin-Arab (BA) population in southern Israel is characterized by a high rate of consanguinity, common hereditary disorders, and transition from a semi-nomadic, traditional society to a more sedentary and urbanized society. In this hospital-based study, the demographic and the clinicopathological characteristics of BC in BA were compared with Jewish patients. MATERIALS AND METHODS: 85 BA patients treated at the Soroka Medical Center, Beer Sheba, during the years 2004-2012, were studied and compared with 180 consecutive Jewish patients treated during the year 2007. Clinicopathological features compared included age, menopausal state, number of births, a history of BC in first-degree relatives, tumor size (T), extent of lymph- node involvement (N), distant metastases (M), stage, grade, estrogen and progesterone receptor (ER/PR), and Her2 status. Types of treatment, relapse rate and site, as well as outcome were also studied. Cox's regression models were applied for studying disease-free, and overall survival. RESULTS: Compared with Jewish patients, BA patients were younger (average age 49±12 yrs vs 59±13, p<0.001), had a lower rate of BC in first-degree relatives (p<0.001), and a larger number of births (6±4.2 vs 2.5±1.9, p<0.001). BA patients had larger tumors (p=0.02), more extensive lymph-node involvement (p=0.002), and more advanced stage (p=0.003). Grade, ER, PR, and Her2 status were similar in the two ethnic groups. Relapse type was most commonly systemic in BA patients (p=0.05), and loco-regional in Jewish patients (p=0.02). Median survival was 63, and 35 months for Jewish and BA patients, respectively (log-rank test, p=0.02). In Cox multivariate analysis, stage and PR status (HR-0.14, p<0.0001; HR-3.11, p=0.046), but not ethnicity, influenced overall survival. CONCLUSIONS: BC presents a decade earlier, and with more advanced disease in BA compared with Jewish patients. Biologic parameters including grade, ER, PR, and Her2 status were similar in both groups. Although prognosis was worse in BA than in Jewish patients, it was affected only by stage and PR status, but not by ethnicity.