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Johnny Kao

Publications and source records attributed to Johnny Kao.

13 recordsLinked to original sources
PubMed2026

Selective Omission of Oncotype Dx Genomic Testing in Ultra-Low-Risk Luminal A Breast Cancer.

INTRODUCTION: Older women with early-stage luminal A breast cancer have an excellent prognosis with a 5-year relative survival >99%. Research on curtailing overtreatment has challenged historical standards of care by reducing radiotherapy dose and volume, and selectively omitting sentinel lymph node biopsy. This study assessed the utility of Oncotype Dx genomic testing in ultra-low-risk luminal A breast cancer. PATIENTS AND METHODS: A community hospital cancer registry was queried to identify consecutive breast cancer patients from 2014 to 2022. An ultra-low-risk population was defined as age ≥60 years, hormone-receptor positive, HER2-negative, pathologic stage T1b-T2N0 without lymphovascular invasion, and Ki-67 ≤13.25%. Analyses examined the distribution of Oncotype Dx scores categorized as low risk (0-18), intermediate risk (19-25), or high risk (26-100), as well as recurrence and overall survival. RESULTS: Of 1711 patients, 91 met ultra-low-risk eligibility criteria with available Oncotype Dx results. The median age was 70 years with a median follow-up of 5.1 years, and no patients received chemotherapy. Only 1 patient (1.1%) had a high-risk Oncotype Dx score of ≥26, while 12 (13.2%) had intermediate scores and 78 (85.7%) were low risk. Five-year local control and overall survival were 100% and 93%, respectively. Ten non-breast cancer deaths occurred, and no patients developed distant metastases. CONCLUSION: We describe a pragmatic method using common clinical and pathological features to define an ultra-low-risk cohort. Older luminal A patients with favorable pathology have a very low probability of receiving a high-risk Oncotype Dx score and demonstrate an excellent prognosis with standard adjuvant therapy.

Chemotherapy↗
PubMed2006

Intensity-modulated radiation therapy in advanced head and neck patients treated with intensive chemoradiotherapy: preliminary experience and future directions.

We review our recent experience with intensity-modulated radiation therapy (IMRT) and conventional three-dimensional radiation therapy (C3DRT) in advanced head and neck cancer. Sixty-nine patients with Stage IV head and neck cancer (and stage III base of tongue and hypopharynx) enrolled in a Phase II study of definitive chemoradiation; 20 received all or part of their radiation with IMRT. Image-guided set-up, using video subtraction techniques, was used in all patients. Six weekly doses of induction carboplatin (AUC=2) and paclitaxel (135 mg/m2) were followed by alternating weekly chemoradiation to 75 Gy with 1.5 Gy BID fractions, concurrent with paclitaxel (100 mg/m2/week), 5-fluorouracil (600 mg/m2/d) and hydroxyurea (500 mg PO BID). Two consecutive cohorts enrolled, differing in radiation scheme: 75 Gy to gross disease in both, 60 or 54 Gy to first echelon lymphatics and 45 or 39 Gy to second echelon lymphatics. With a median follow-up of 47 months, 3-year overall survival is 68.5% and 3-year locoregional control is 94.0%, with no significant differences between those treated with C3DRT versus IMRT, nor between the two radiation dosing schemes. Actuarial overall survival without tracheostomy or laryngectomy, or without a gastrostomy tube was also similar. Acute mucositis, dermatitis and pain were similar with C3DRT and IMRT. Preliminary data suggests IMRT is well tolerated, and does not compromise locoregional control, indicating that IMRT adequately covers the clinical volume at risk. Building on the present clinical experience, future directions include more directed efforts at reducing toxicity, with better planning software and planning techniques.

Adult↗
PubMed2005

Long-term outcome of concurrent chemotherapy and reirradiation for recurrent and second primary head-and-neck squamous cell carcinoma.

PURPOSE: To define favorable pretreatment characteristics for overall survival (OS), progression-free survival (PFS), locoregional control, and freedom from distant metastasis for patients with recurrent and second primary head-and-neck cancer treated with concomitant chemotherapy and reirradiation. METHODS AND MATERIALS: Our study population comprised a subset of 115 previously irradiated patients without overt metastases from 304 poor-prognosis head-and-neck cancer patients treated in seven consecutive phase I-II protocols. Of the 115 patients, 49, who had undergone surgical resection, were treated with a median of four cycles of concurrent chemotherapy and reirradiation and 66, who had not undergone surgical resection, were treated with a median of five cycles. The following regimens were used: 5-fluorouracil and hydroxyurea concurrent with reirradiation (FHX) (n=14), cisplatin plus FHX (n=23), paclitaxel plus FHX (n=42), gemcitabine plus paclitaxel and 5-fluorouracil concurrent with reirradiation (n=26), and irinotecan plus FHX (n=10). RESULTS: The median lifetime radiation dose was 131 Gy. The median follow-up for surviving patients was 67.4 months (range, 18.5-158.7). The median OS and PFS was 11 and 7 months (range, 0.2-158.7), respectively. The 3-year OS, PFS, locoregional control, and freedom from distant metastasis rate was 22%, 33%, 51%, and 61%, respectively. Multivariate analysis identified reirradiation dose, triple agent (cisplatin-, paclitaxel-, or gemcitabine-containing chemotherapy), and surgery before protocol treatment as independently prognostic for OS, PFS, and locoregional control. Triple-agent chemotherapy was prognostic for freedom from distant metastasis. Nineteen patients died of treatment-related toxicity, five of these of carotid hemorrhage. CONCLUSION: For recurrent and second primary head-and-neck cancer, trimodality therapy with surgery, concurrent chemotherapy, and reirradiation for a full second dose offers potential for long-term survival. Owing to the substantial toxicity and lack of an optimal regimen, reirradiation of recurrent head-and-neck cancer should be limited to clinical trials.

Adult↗
PubMed2005

Postprostatectomy adjuvant versus salvage radiotherapy: a complication-adjusted number-needed-to-treat analysis.

BACKGROUND: Radiotherapy (RT) has been used with success after radical retropubic prostatectomy (RRP), both in the adjuvant and salvage settings. The purpose of the current investigation was to systematically compare adjuvant versus salvage RT in a manner that incorporates both treatment efficacy and complications. METHODS: A literature review was performed of reports of post-RRP salvage and adjuvant RT, and 12 trials comprising 1060 patients met the appropriate inclusion criteria. The biochemical failure-free survival in each study/arm was tabulated, and these values were entered into a model to compute an unadjusted number-needed-to treat (NNT). RT complications were then considered, accounting for differences in toxicity incidences in the salvage versus adjuvant setting, to compute complication-adjusted NNTs. In all the trials, the signs and magnitudes of the NNTs obtained were used to compare adjuvant with salvage RT. RESULTS: The absolute NNT analysis showed an advantage of adjuvant compared with salvage RT. After adjustment for RT complications, however, the advantage shifted to salvage RT. This transition point from superiority of adjuvant RT to superiority of salvage RT was sensitive to the estimated incidence and severity of RT side effects. CONCLUSIONS: Adjuvant post-RRP RT was advantageous in comparison to salvage RT if the side effects of RT were estimated to be negligible. However, with moderate incidence/severity of RT side effects, salvage RT was advantageous. The findings herein must be tested in a prospective study in which both health-related quality of life and cancer control are documented in patients receiving adjuvant versus salvage post-RRP RT. Further work is needed to better estimate parameters entered into the model to determine the precise transition point between adjuvant and salvage RT with modern RT techniques.

Humans↗
PubMed2005

Concomitant radiation therapy and paclitaxel for unresectable locally advanced breast cancer: results from two consecutive phase I/II trials.

PURPOSE: The management of unresectable locally advanced breast cancer (ULABC) remains a major challenge because of the necessity both to treat local disease and to prevent distant disease. Two consecutive Phase I/II trials of concomitant chemotherapy and radiation (CRT) were performed to attempt to address both local and distant disease control in ULABC. This analysis focuses on rates of locoregional control and radiation-associated acute and late complications. METHODS AND MATERIALS: Thirty-three patients with unresectable locally advanced or inflammatory breast cancers (T4N0-3M0-1) or locally recurrent disease were treated with CRT on two consecutive Phase I/II trials. Radiotherapy consisted of 60-70 Gy to the breast or chest wall and 60 Gy to draining lymphatics in a week-on/week-off (WO/WO) schedule. Chemotherapy consisted of either continuous infusion or bolus paclitaxel +/- vinorelbine. A subset analysis of 16 patients with nonmetastatic ULABC Stage IIIB-C (T4N0-3M0) was performed. Among this cohort, 13 patients (81%) underwent planned mastectomy after CRT. RESULTS: Of the 16 patients with Stage IIIB-C disease, acute toxicity included moist desquamation (n = 8) and Grade 3-4 neutropenia (n = 3). Late toxicity included breast reconstruction loss, decreased range of arm motion, lymphedema, and skin toxicity, although none was life-threatening. Of 15 assessable patients, 14 had a clinical response, 7 had a pathologic complete response (pCR) including 6 of 13 patients undergoing mastectomy. With a median follow-up for living patients of 43.8 months, the 4-year actuarial locoregional control, disease-free survival, and overall survival were 83%, 33%, and 56% respectively. CONCLUSIONS: Concurrent WO/WO radiation therapy and paclitaxel +/- vinorelbine is effective locoregional therapy for ULABC with an acceptable toxicity profile. Further investigation of concurrent chemoradiotherapy in ULABC is warranted.

Adult↗
PubMed2005

Twice-daily reirradiation for recurrent and second primary head-and-neck cancer with gemcitabine, paclitaxel, and 5-fluorouracil chemotherapy.

PURPOSE: We previously demonstrated the efficacy of concurrent gemcitabine, paclitaxel, and 5-fluorouracil in conjunction with twice-daily (1.5-Gy) radiotherapy delivered on alternating weeks (TFGX(2)) in locally advanced head-and-neck cancer. Here, we report the clinical outcome and late toxicity of TFGX(2) in a subset of patients previously irradiated to the head and neck. METHODS AND MATERIALS: Twenty-nine previously irradiated patients, presenting with recurrent or second primary head-and-neck cancer, underwent TFGX(2). Twelve patients underwent attempted surgical resection before chemoradiotherapy, 10 of whom were left with no measurable disease. Patients with measurable disease received a median radiation dose of 72 Gy; those with no measurable disease received a median dose of 61 Gy. The cumulative dose ranged from 74.4 to 156.4 Gy (mean, 125.7 Gy; median, 131.0 Gy). RESULTS: The median follow-up was 19.1 months (50.9 months for living patients). The 5-year overall survival rate was 34.5%, and the locoregional control rate was 54.5%. In patients with measurable disease at treatment, the 5-year overall survival and locoregional control rate was 26.3% and 45.1%, respectively, compared with 50.0% (p = 0.14) and 70% (p = 0.31), respectively, for those with no measurable disease. Measurable disease and radiation dose were highly statistically significant for overall survival and locoregional control on multivariate analysis. Of 14 patients assessable for late toxicity, 3 developed Grade 4-5, 8 Grade 2-3, and 3 Grade 0-1 toxicity. CONCLUSION: Aggressive reirradiation with chemotherapy in locally advanced head-and-neck cancer provides a chance for long-term cure at the expense of toxicity. Attempted surgical resection before chemoradiotherapy improved disease control and survival.

Adult↗
PubMed2005

Hormone therapy and radiotherapy for early prostate cancer: a utility-adjusted number needed to treat (NNT) analysis.

PURPOSE: To quantify, using the number needed to treat (NNT) methodology, the benefit of short-term (< or =6 months) hormone therapy adjuvant to radiotherapy in the group of patients with early (clinical stage T1-T2c) prostate cancer. METHODS AND MATERIALS: The absolute biochemical control benefit for the use of hormones adjuvant to radiotherapy in early-stage disease was determined by literature review. A model was developed to estimate the utility-adjusted survival detriment due to the side effects of hormone therapy. The NNTs before and after the incorporation of hormone sequelae were computed; the sign and magnitude of the NNTs were used to gauge the effect of the hormones. RESULTS: The absolute NNT analysis, based on summarizing the results of 8 reports including a total of 3652 patients, demonstrated an advantage to the addition of hormones for the general early-stage prostate cancer population as well as for all prognostic groups. After adjustment for hormone-induced functional loss, the advantage of hormones remained considerable in the high- and intermediate-risk groups, with the utility-adjusted NNT becoming weakened in the low-risk group when the utility compromise from complications of hormones was assumed to be considerable. CONCLUSIONS: Short-term hormone therapy seems to be beneficial for selected early-stage prostate cancer patients. The advantage seems to be greatest in the intermediate- and high-risk groups; with current follow-up, the side effects of hormones may outweigh their benefit in certain clinical situations in the favorable group. The present investigation demonstrates the significant role of the NNT technique for oncologic and radiotherapeutic management decisions when treatment complications need to be considered and balanced with the beneficial effects of the treatment.

Androgen Antagonists↗
PubMed2005

Does the number of lymph nodes examined in patients with lymph node-negative breast carcinoma have prognostic significance?

BACKGROUND: There are conflicting data on the prognostic significance of the number of lymph nodes examined in patients with lymph node-negative breast carcinoma. Therefore, the authors analyzed the impact of the number of tumor-free axillary lymph nodes on disease-free survival (DFS) in two distinct patient populations. METHODS: Eight hundred thirty-three consecutive patients with breast carcinoma who underwent mastectomy between 1927 and 1987 and 1094 consecutive patients with breast carcinoma who underwent with breast-conservation therapy between 1984 and 2001 were diagnosed pathologically with negative axillary lymph node status. Patients were stratified into 4 groups according to the number of lymph nodes examined: Group 1 had 1-3 lymph nodes examined, Group 2 had 4-9 lymph nodes examined, Group 3 had 10-20 lymph nodes examined, and Group 4 had >20 lymph nodes examined. RESULTS: In the mastectomy cohort, with a median follow-up of 153 months, the 10-year DFS rate was 70%, 65%, 79%, and 81% for Groups 1-4, respectively. On multivariate analysis, pathologic tumor size (P<0.001) and the number of lymph nodes examined (P=0.010) were significant predictors for long-term DFS. In the breast-conservation cohort, with a median follow-up of 53 months, the 5-year DFS rate was 90%, 91%, 92%, and 95% for Groups 1-4, respectively. On multivariate analysis, the only predictors of DFS were method of detection (clinically vs. mammographically) (P=0.003) and tumor size (P=0.035). CONCLUSIONS: The recovery of <10 lymph nodes in lymph node-negative patients who underwent mastectomy resulted in a 10-15% decreased long-term DFS rate compared with patients who had a more extensive axillary assessment. However, the number of lymph nodes examined did not have an impact on the DFS rate in a contemporary cohort of patients who underwent breast-conservation therapy, which included radiation.

Adult↗
PubMed2005

Cellular response to DNA damage.

Eukaryotic cells, from yeast to man, possess evolutionarily conserved mechanisms to accurately and efficiently repair the overwhelming majority of DNA damage, thereby ensuring genomic integrity. Important repair pathways include base excision repair, nucleotide excision repair, mismatch repair, non-homologous end-joining, and homologous recombination. Defects in DNA repair processes generally result in susceptibility to cancer and, often, abnormalities in multiple organ systems. While signal transduction pathways have been intensely studied, epigenetic changes occurring in response to DNA damage are rapidly increasing in importance. Effective radiation and chemotherapy sensitization could result from selective inhibition of DNA repair in tumor cells. DNA damage repair is a dynamic field of research where the fruits of basic research often have important clinical implications.

DNA↗
PubMed2004

Is there an association between multiple myeloma and prostate cancer?

In a series of 700 consecutive patients with prostate cancer, four patients were noted to have a history of multiple myeloma. An association between prostate cancer and multiple myeloma had not been previously described. An exploratory investigation of the biological basis of these two malignancies was undertaken to determine a possible mechanism for this association. A review of the genetic, molecular and chemical basis of prostate cancer and multiple myeloma development and progression is presented. A model suggesting the possible impact of immunosuppression from multiple myeloma and chemokines released by circulating myeloma cells including IGF-1, IL6, SDF1 and VEGF on the progression of prostate cancer to detectable stages is presented.

Chemokine CXCL12↗
PubMed2003

Hormone therapy adjuvant to external beam radiotherapy for locally advanced prostate carcinoma: a complication-adjusted number-needed-to-treat analysis.

BACKGROUND: Hormone therapy commonly is used to treat metastatic, locally advanced, and localized prostate carcinoma. The objective of the current investigation was to determine, using the number-needed-to-treat (NNT) method, the effect of using hormone therapy to treat locally advanced disease, with consideration given to both the complications and the known advantages associated with hormone therapy. METHODS: A literature review was performed to determine 1) the absolute benefit, based on available clinical endpoints, associated with the addition of hormone therapy to external beam radiotherapy for locally advanced prostate carcinoma; 2) the incidence of side effects of short-term and long-term hormone therapy; and 3) the stepwise progression from biochemical failure to death. A model was constructed to estimate the complication/utility-adjusted survival detriment resulting from the side effects of short-term (</= 6 months) and long-term (> 6 months) hormone therapy, and the absolute/unadjusted and complication-adjusted NNTs for the addition of short-term and long-term hormone therapy were computed. In all cases, the magnitudes and signs of the NNTs obtained were used to gauge the effect of hormone therapy. RESULTS: The unadjusted NNTs were positive and in most cases had relatively small magnitudes (the greater the NNT, the smaller the benefit) for both short-term and long-term hormone therapy; these results were expected, and they suggested that there is a strong benefit associated with the use of hormones adjuvant to radiotherapy for locally advanced disease. Adjusted NNTs remained positive and had relatively small magnitudes even after the introduction into the analysis of complications of short-term and long-term hormone therapy. This finding, although weak with respect to the effect of short-term hormone therapy on cause-specific survival, remained robust over the range of values for utility impairment expected from short-term and long-term hormone therapy. CONCLUSIONS: The benefits of short-term and long-term hormone therapy for locally advanced prostate carcinoma appear to be significant and to outweigh the associated side effects. Long-term therapy appears to be better than short-term therapy in terms of virtually all endpoints studied, even when the increased incidence of side effects is considered. The current investigation was successful in the use of the complication-adjusted NNT method for oncologic and radiotherapeutic scenarios in which the results of randomized trials could be summarized, adjusted for treatment toxicity, and individualized to a given patient.

Antineoplastic Agents, Hormonal↗
PubMed2003

Reirradiation of recurrent and second primary head and neck malignancies: a comprehensive review.

The management of locoregionally recurrent or second primary tumors in a previously irradiated head and neck volume presents a challenging clinical problem. Only a small subset of patients are candidates for potentially curative surgery. Chemotherapy alone provides only limited palliation with no long term survivors. Reirradiation, particularly with aggressive concomitant chemotherapy, results in prolonged median survival and long term survival for some patients. The toxicity of reirradiation, while greater than chemotherapy alone or primary irradiation, is lower than expected for the high cumulative radiation doses. The results of reirradiation in recurrent head and neck cancer and the prognostic factors predicting outcome in this patient population are reviewed.

Antineoplastic Combined Chemotherapy Protocols↗