Severity Of Skin Toxicity Research Articles

Skin dose effects of postmastectomy chest wall radiation therapy using brass mesh as an alternative to a bolus.

157 Background: The use of brass mesh as an alternative to a bolus is relatively uncommon in post-mastectomy chest wall radiation therapy (PMRT). This study aimed to characterize the skin dose effects of using 2mm fine brass mesh as an alternative to the traditional tissue-equivalent bolus during chest wall PMRT. Methods: Data was collected from patients who received PMRT using brass mesh at UC Davis Medical Center’s Department of Radiation Oncology between January 2008 and June 2011. Several patient characteristics including age, body habitus, and ethnicity were analyzed along with several disease and treatment characteristics to determine whether or not they had an impact on the skin reaction observed during radiation treatment. In addition to assessing skin toxicity visually using standardized National Cancer Institute scores (NCIS), surface doses were measured for 16 of the 48 patients (33%) to quantify radiation exposure to the chest wall. Results: 48 female patients aged 28-83 received PMRT using brass mesh. As expected, the severity of skin toxicity increased with subsequent doses of radiation with all patients beginning treatment with no skin reaction (NCIS = 0) and the majority of patients completing treatment with either faint to moderate erythema (N = 19, 40%, NCIS = 1) or moderate to brisk erythema (N = 23, 48%, NCIS = 2). In vivo dosimetry analysis revealed surface doses between 81% and 110% of the prescribed dose, with an average of 99% of the prescribed radiation dose being delivered and a standard deviation of 10%. Conclusions: For post-mastectomy chest wall radiation therapy, brass mesh is an effective alternative to the tissue-equivalent bolus. The brass mesh achieved moderate erythema in the majority of patients at the end of treatment and the surface dose was validated using in vivo dosimetry.

Skin dose effects of postmastectomy chest wall radiation therapy using brass mesh as an alternative to tissue equivalent bolus

PurposeThe use of brass mesh as a bolus is relatively uncommon in postmastectomy chest wall radiation therapy (PMRT). This study aimed to characterize the skin dose effects of using 2-mm fine brass mesh as an alternative to the traditional tissue-equivalent bolus during chest wall PMRT. Methods and MaterialsData were collected from patients who received PMRT using brass mesh at the University of California Davis Department of Radiation Oncology between January 2008 and June 2011. Several patient characteristics including age, body habitus, and ethnicity were analyzed along with several disease and treatment characteristics to determine whether or not they had an impact on the skin reaction observed during radiation treatment. Additionally, in vivo surface dose measurements were obtained for 16 of the 48 patients (33%). ResultsForty-eight female patients aged 28-83 received PMRT using brass mesh. As expected, the severity of skin toxicity increased with subsequent doses of radiation with all patients beginning treatment with no skin reaction (National Cancer Institute scores [NCIS] = 0) and the majority of patients completing treatment with either faint to moderate erythema (n = 19, 40%, NCIS = 1) or moderate to brisk erythema (n = 23, 48%, NCIS = 2). In vivo dosimetry analysis revealed surface doses between 81% and 122% of the prescribed dose, with an average of 99% of the prescribed radiation dose and standard deviation of 10% being delivered. ConclusionsFor postmastectomy chest wall radiation therapy, brass mesh is an effective alternative to tissue-equivalent bolus. The brass mesh achieved moderate erythema in the majority of patients at the end of treatment and the surface dose was validated using in vivo dosimetry.

Histopathologic and Immunohistochemical Characterization of Rash to Human Epidermal Growth Factor Receptor 1 (HER1) and HER1/2 Inhibitors in Cancer Patients

Human epidermal growth factor receptor (HER) 1 and HER 1/2 inhibitors have shown benefit against a wide range of solid tumors. However, their use is associated with rash in 40% to 90% of patients, which impacts quality of life and interrupts antineoplastic therapy. The pathologic characteristics of affected skin remain unclear, precluding development of rational therapies. The aim of this study was to evaluate differences in histologic and immunohistochemical alterations in rash caused by lapatinib, a dual HER1/2 inhibitor (HER1/2i), and the single HER1 inhibitors (HER1i) cetuximab, erlotinib, and panitumumab. For each of the four drugs, skin biopsies were collected and analyzed from 8 patients with rash (n = 32). Blinded independent histologic analysis and automated measurement of 17 skin biomarkers involved in proliferation, differentiation, and inflammation were conducted. Increased expression of pAKT and decreased dermal K16 and p27 for HER1/2i when compared with each of the HER1i were observed. In addition, decreased epidermal atrophy and follicular neutrophilic infiltrate were evidenced in the skin of patients on HER1/2i when compared with HER1i. We found a lower inhibition of epidermal kinetics and decreased inflammation in HER1/2i-induced rash. These findings underscore differences in skin toxicity as related to specificity of HER blockade, concordant with clinical tolerability and decreased severity of skin toxicity seen with the HER1/2i lapatinib compared with the HER1 inhibitors cetuximab, erlotinib, and panitumumab.

Expert Consensus on the Management of Erlotinib-Associated Cutaneous Toxicity in the U.K.

Rash has been reported in up to 76% of patients with lung cancer who have received the epidermal growth factor receptor inhibitor (EGFRI) erlotinib. It has also been observed in patients treated with other agents that have a similar mode of action. Erlotinib-associated skin toxicity typically presents as a papulopustular, follicular, acneiform rash. In most cases, it is mild, transient, and well tolerated, but in 8%-12% of patients, it may be sufficiently severe and persistent to necessitate intervention. Increasingly strong data suggest that the incidence and severity of skin toxicity may be predictive of response and survival in patients treated with erlotinib. This has prompted some clinicians to consider "treatment to rash" (i.e., increasing the dosage until a rash appears) as a rational management strategy. In 2007, an international consensus was developed for the management of EGFRI-associated skin toxicity. Subsequently, a multidisciplinary group (the U.K. Erlotinib Skin Toxicity Management Consensus Group) met to validate and modify the international recommendations for U.K. use, with specific reference to erlotinib. Although many aspects of the international consensus were approved by the group as being relevant for the U.K., certain parts were modified. The resulting expert opinion is a practical and workable version of the international proposal that considers all applicable national issues regarding the management of erlotinib-associated skin toxicity.

Characteristics and outcomes of non-small cell lung cancer (NSCLC) patients (pts) carrying epidermal growth factor receptor (EGFR) mutations who progress after initial erlotinib (E) response

8064 Background: Most NSCLC pts with EGFR mutations respond to E; however, resistance to this tyrosine kinase inhibitor (TKI) can be acquired. The resistant T790M mutation has been identified in 50% of progressing pts. We assessed pt characteristics and outcome to additional treatment in 55 EGFR mutated pts after progression to E. Results: Pts mean age was 59±12.5 years; 65% females; 94% never-smokers; 54 adenocarcinoma. 35 pts (63%) were PS ≤2; main metastasis sites were lung (39/71%), bone (21/38%) and liver (10/18%). 22 and 25 pts received E as first- or second-line treatment, respectively. Mutations in tumor were: 65% DelE19 (Δ746–750), 35% L858R mutation; with 31% and 20% serum detection respectively. For the complete cohort, overall response rate (ORR) with E was 78% and time to progression (TTP) was 11.2 months (m) (range, 4–29 m). After progressing to E, 8 pts were re-biopsied, of whom 2 had the T790M mutation; 9 had the T790M mutation in serum (16%). 49% received platinum-based chemotherapy, 14.5% E plus another agent (bevacizumab, fulvestrant, vorinostat), 25.5% single-agent chemotherapy and 11% a non-reversible TKI (HKI-272). ORR for first-line post-E treatments was 33% (CR 1/PR 9) and median TTP was 8 m (range, 4.1–11.8 m). There were no differences in TTP according to gender (p = 0.10), type of mutation (p = 0.63) or severity of skin toxicity (p = 0.16). 11 pts received a second-line post-E treatment with E plus chemotherapy, achieving an ORR of 40%. Median survival was 27 m for all 55 pts (range, 22.9–31.1 m). Conclusions: Pts with EGFR mutations present a biologically different disease which continued to be sensitive to other treatments after progressing to E. No significant financial relationships to disclose.

Analysis of Factors Influencing Skin Toxicity after Autologous Hematopoeitic Stem Cell Transplant.

Skin toxicity is a known but understudied complication of autologous stem cell transplantation (ASCT). Its assessment is complicated by the development of graft-vs-host disease following allogeneic transplantation. We chose therefore to study skin toxicity following autologous transplantation. We retrospectively reviewed the records of 392 patients undergoing ASCT to analyze risk factors for skin toxicity, its association with mucositis and its effect on survival. Skin toxicity was assessed three times a week during the transplant admission and was classified as none, mild, moderate, severe or life threatening. The most severe skin toxicity is used in this analysis. Mucositis was assessed using the modified oral mucositis assessment scale (OMAS). Median patient age was 53 years; 63% of patients had non-Hodgkin s lymphoma (NHL), 17.6% multiple myeloma, 13.5% Hodgkin disease (HD) and 5.9% acute leukemia. Peripheral blood progenitor cells were mobilized with G-CSF alone (36%) or the combination of etoposide plus G-CSF (64%). The preparative regimen was busulfan (Bu)/cyclophosphamide (Cy) /etoposide in 82% and Bu/Cy alone in 18%. Two hundred and sixty patients (67%) developed skin toxicity of which 143 patients (36.5%) had mild, 105 (26.8%) had moderate and 16 (3.9%) had severe skin toxicity. Factors associated with the development of any skin toxicity in univariable analysis were male gender (p=0.028), diagnosis of NHL (p<0.001) or HD (p=0.001), higher number of prior chemotherapy regimens (p<0.001), mobilization regimen containing etoposide (p< 0.001) and ASCT preparative regimen containing etoposide (p<0.001). Moderate skin toxicity correlated with the above as well. Only the inclusion of etoposide in the mobilization regimen was associated with an increased risk of severe skin toxicity (p=0.035). Etoposide in the preparative regimen remained the most significant risk factor for the development of skin toxicity in multivariable analysis. Higher OMAS score was associated with increased severity of skin toxicity (p<0.001) as shown in the boxplot below:Patients with severe skin toxicity appeared to have worse overall survival (p=0.054) and relapse-free survival (p=0.08), but these findings did not reach statistical significance.Conclusion: A substantial proportion of patients develop skin toxicity following autotransplantation. The inclusion of etoposide in the preparative regimen is associated with a significant increased frequency in multivariable analysis. The severity of skin toxicity correlates closely with the severity of mucositis. [Display omitted]

Predictive value of skin toxicity severity for response to panitumumab in patients with metastatic colorectal cancer (mCRC): A pooled analysis of five clinical trials

4134 Background: Panitumumab, a fully human monoclonal antibody against the epidermal growth factor receptor (EGFr), is approved for EGFr-expressing mCRC patients (pts) with disease progression (PD) on or following fluoropyrimidine (5FU)-, oxaliplatin (Ox)-, and irinotecan (Ir)-containing chemotherapy. Skin toxicities are common with panitumumab; we examined the association between severity of skin toxicity and panitumumab efficacy. Methods: Data from 5 clinical trials were pooled (4 phase II studies and 1 phase III study). Pts with mCRC had documented PD on or after 5FU, Ox, and/or Ir. Pts received panitumumab 6 mg/kg every two weeks (Q2W) or 2.5 mg/kg weekly (QW) until PD or intolerability. Tumors were assessed using modified WHO or RECIST criteria (blinded central review in 4/5 studies). Endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). PFS and OS were measured from enrollment. Only pts with =2 infusions (exposure over 2 wks for QW dosing or over 4 weeks for Q2W dosing) were analyzed to help correct for lead-time bias. Results: 612 of 640 pts were included in the analysis set (62% were male, 92% were white, and median age [range] was 61 [21, 88] years). The median (95% CI) duration of PFS was 8.4 weeks (8.0 to 11.3), the median (95% CI) survival was 6.9 months (6.2 to 7.9), and the ORR (95% CI) was 9.0% (6.8 to 11.5). The most common skin toxicities (any grade, grade 3/4) were erythema (54%, 4%) pruritus (53%, 2%), dermatitis acneiform (52%, 5%), and rash (39%, 2%). ORR, PFS, and OS appeared to favor pts with grade 2–4 skin toxicity vs pts with grade 0- 1 skin toxicity ( table ). Conclusion: In this large combined analysis, severity of skin rash was correlated with increased efficacy of panitumumab in terms of ORR, PFS, and OS. [Table: see text] No significant financial relationships to disclose.

Cetuximab and irinotecan as third line therapy in patients with advanced colorectal cancer after failure of irinotecan, oxaliplatin and 5-fluorouracil

Cetuximab (Erbitux®) in combination with irinotecan is the most promising combination in heavily pretreated patients with advanced colorectal cancer. Efficacy of this combination was confirmed in the pivotal BOND I study. The aim of the present study was to evaluate efficacy and toxicity of a combination regimen of cetuximab and irinotecan but in contrast to the BOND I study all patients had previously received 5-FU, oxaliplatin and irinotecan and all had progressed during or shortly after completion of treatment. Before January 2005 salvage therapy with cetuximab and irinotecan was not used in Denmark. The Danish government had initiated a national programme for patients with advanced cancer and according to this programme the National Board of Health may approve and finance experimental treatment. From January 2005 to September 2005, 65 consecutive patients were treated with cetuximab (weekly) and irinotecan (each 2 or 3 weeks) at three university hospitals. Median age was 57 years (23–78), and median performance status was 1 (0–3). Response rate was 20%, median TTP was 5.5 months and median OS was 10.4 months. Response and survival was significantly correlated with severity of skin toxicity. Toxicity grade 3 was rare (skin toxicity 8%, diarrhoea 10%, nausea 3%, vomiting 3%, fatigue 8%). Salvage therapy with cetuximab and irinotecan is effective in patients pretreated with irinotecan, and oxaliplatin and in a general population the results from the BOND I study was confirmed.

Gefitinib is active in patients with brain metastases from non-small cell lung cancer and response is related to skin toxicity

Gefitinib is active and well tolerated in patients with advanced non-small cell lung cancer (NSCLC); however, its role in patients with brain metastases has not been clearly defined. We had conducted a prospective study to give gefitinib to NSCLC patients irrespective of their performance status (PS), number of prior treatment regimens and the presence of brain metastases. A total of 76 patients were enrolled. Fifty-seven patients had measurable lesions and the objective response rate was 33.3% (95% confidence interval [95% CI], 20.7–46.0%). For all enrolled patients, the disease control rate was 63.2% (95% CI, 52.1–74.3%) with a median progression-free survival of 5.0 months (95% CI, 3.6–6.5 months) and median overall survival 9.9 months (95% CI, 4.9–14.8 months). Twenty-one patients had simultaneously assessable intracranial lesions (ICLs) and extracranial lesions (ECLs), 17 of them (81.0%) showed comparable tumor response. There was no survival difference between the patients with and without metastatic brain disease. Most drug-related adverse events were mild. Intolerable toxicities happened in five patients, four of them were interstitial pneumonia (5.8%). Severity of skin toxicity was tightly associated with tumor response and patient survival ( P = 0.007 and <0.001) and the association was consistent in the analysis using early toxicity profile ( P = 0.033 and 0.001). In conclusion, gefitinib is active in patients with brain metastasis from NSCLC and tumor response is related to skin toxicity. It is feasible to conduct randomized trials to identify the role of gefitinib alone or in combination with other modality for treatment of NSCLC patients who have metastatic brain lesion(s).